Is FTCD p.Ala438Val (c.1313C>T) pathogenic?

FTCD p.Ala438Val (c.1313C>T) is classified Benign in FTCD (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-28). AlphaMissense: likely benign (0.0829); Common (popmax 11.1%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with formiminoglutamic aciduria.

What condition is associated with FTCD p.Ala438Val (c.1313C>T)?

FTCD p.Ala438Val (c.1313C>T) is associated with formiminoglutamic aciduria (ClinVar).

How is Formiminoglutamic aciduria inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about FTCD p.Ala438Val (c.1313C>T)?

AlphaMissense predicts likely benign (score 0.0829) — an in-silico prediction, not a clinical call.

FTCD p.Ala438Val

Q: How common is FTCD p.Ala438Val (c.1313C>T) in the general population?

FTCD p.Ala438Val (c.1313C>T) is common (popmax 11.1%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1313C>T · rs61735841 · VCV95423

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0829 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 11.1%, nfe) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

formiminoglutamic aciduria

Computational evidence

Protein change
AlphaMissense	0.0829	likely benign
REVEL	0.048	moderately benign-leaning
SaProt	LLR -7.68	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.6	GERP -2, phastCons 0.85
Regional constraint	o/e 1.12	unconstrained · MANE · 19 kb · p 0.00063 · regional, not allelic
Overall
CADD	13.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 11.1% European (non-Finnish) · 130,032/1,175,656 alleles

Filtering AF 11% ClinGen BA1/BS1 input FAF95, joint · FAF99 11%

Overall 9.19% 146,307/1,592,622 alleles · common exomes 136,266/1,440,316 · genomes 10,041/152,306 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	11.1%	9
Amishnot grpmax-eligible	9.01%	11
Remaining individualsnot grpmax-eligible	8.56%	12
Ashkenazi Jewishnot grpmax-eligible	6.21%	16
Finnishnot grpmax-eligible	6%	17
Middle Eastern	5.29%	19
Admixed American	3.87%	26
African / African-American	2.14%	47
South Asian	1.88%	53
East Asian	0.394%	254

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: FTCD
Protein: p.Ala438Val
Coding: c.1313C>T
MANE Select: NM_206965
dbSNP: rs61735841
Type: single nucleotide variant
Location: chr21:46138638 (GRCh38)
Gene constraint: LOEUF 1.61 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 95.30
Residue 438: a UniProt-annotated variant site (sequence variant); the 'cyclodeaminase/cyclohydrolase' region

Full FTCD gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

formiminoglutamic aciduria — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Formiminoglutamic aciduria (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood

Similar variants

FTCD p.Ala438Thr Uncertain significance ★ ⚠ same residue
FTCD p.Ala438= Likely benign ★ same residue
FTCD p.Arg255Ter Pathogenic ★★ same condition
FTCD p.Arg71Ter Pathogenic/Likely pathogenic ★★ same condition
FTCD p.Leu536Ter Pathogenic/Likely pathogenic ★★ same condition
FTCD p.Ala108Thr Uncertain significance ★★ ⚠ same condition
FTCD p.Ala159Val Uncertain significance ★★ ⚠ same condition
FTCD p.Ala368Val Uncertain significance ★★ ⚠ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/ftcd-p-ala438val (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown