Is FTCD p.Val101Met (c.301G>A) pathogenic?

FTCD p.Val101Met (c.301G>A) is classified Benign in FTCD (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-31). AlphaMissense: likely benign (0.0532); Common (popmax 14%, eas) — too common for a highly-penetrant pathogenic allele; Associated with formiminoglutamic aciduria.

What condition is associated with FTCD p.Val101Met (c.301G>A)?

FTCD p.Val101Met (c.301G>A) 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.Val101Met (c.301G>A)?

AlphaMissense predicts likely benign (score 0.0532) — an in-silico prediction, not a clinical call.

FTCD p.Val101Met

Q: How common is FTCD p.Val101Met (c.301G>A) in the general population?

FTCD p.Val101Met (c.301G>A) is common (popmax 14%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.301G>A · rs61735836 · VCV340441

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.0532 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 14%, eas) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

formiminoglutamic aciduria

Computational evidence

Protein change
AlphaMissense	0.0532	likely benign
REVEL	0.197	benign-leaning
SaProt	LLR -1.10	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 3.9	GERP 0.42, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 19 kb · p 0.00063 · regional, not allelic
Overall
CADD	14.39	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 14% East Asian · 5,869/41,850 alleles

Filtering AF 13.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 13.6%

Overall 4.92% 76,536/1,556,074 alleles · common exomes 67,962/1,403,764 · genomes 8,574/152,310 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	14%	7
South Asian	6.78%	15
African / African-American	6.56%	15
Finnishnot grpmax-eligible	5.96%	17
Remaining individualsnot grpmax-eligible	4.98%	20
European (non-Finnish)	4.41%	23
Middle Eastern	4.29%	23
Ashkenazi Jewishnot grpmax-eligible	3.82%	26
Amishnot grpmax-eligible	2.85%	35
Admixed American	2.85%	35

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.Val101Met
Coding: c.301G>A
MANE Select: NM_206965
dbSNP: rs61735836
Type: single nucleotide variant
Location: chr21:46152973 (GRCh38)
Gene constraint: LOEUF 1.61 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 95.30
Residue 101: the 'formiminotransferase n-subdomain' 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.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
FTCD p.Ala418Thr Uncertain significance ★★ ⚠ same condition
FTCD p.Ala455Thr 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-val101met (accessed [today's date]).

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