Is FTCD p.Glu128Lys (c.382G>A) pathogenic?

FTCD p.Glu128Lys (c.382G>A) is classified Benign in FTCD (ClinVar, Single submitter, 3 submitters; last evaluated 2025-12-01). AlphaMissense: likely benign (0.1162); Rare (popmax 0.263%, nfe); Associated with formiminoglutamic aciduria.

What condition is associated with FTCD p.Glu128Lys (c.382G>A)?

FTCD p.Glu128Lys (c.382G>A) is associated with formiminoglutamic aciduria, intellectual disability (ClinVar).

How common is FTCD p.Glu128Lys (c.382G>A) in the general population?

FTCD p.Glu128Lys (c.382G>A) is rare (popmax 0.263%, nfe) (gnomAD).

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.Glu128Lys (c.382G>A)?

AlphaMissense predicts likely benign (score 0.1162) — an in-silico prediction, not a clinical call.

FTCD p.Glu128Lys

c.382G>A · rs61729373 · VCV340437

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1162 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.263%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

formiminoglutamic aciduria

Computational evidence

Protein change
AlphaMissense	0.1162	likely benign
REVEL	0.211	benign-leaning
SaProt	LLR -6.56	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 3.1	GERP 0.041, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 19 kb · p 0.00063 · regional, not allelic
Overall
CADD	22.0	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 0.263% European (non-Finnish) · 3,045/1,156,458 alleles

Filtering AF 0.255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.252%

Overall 0.215% 3,368/1,566,986 alleles · rare exomes 3,141/1,414,650 · genomes 227/152,336 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.263%	380
Finnishnot grpmax-eligible	0.174%	576
Remaining individualsnot grpmax-eligible	0.147%	682
Amishnot grpmax-eligible	0.11%	912
Ashkenazi Jewishnot grpmax-eligible	0.108%	929
South Asian	0.0585%	1,711
Admixed American	0.0357%	2,800
African / African-American	0.0298%	3,360
East Asian	0.019%	5,276

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.Glu128Lys
Coding: c.382G>A
MANE Select: NM_206965
dbSNP: rs61729373
Type: single nucleotide variant
Location: chr21:46151966 (GRCh38)
Gene constraint: LOEUF 1.61 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 95.30
Residue 128: 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

Also linked: intellectual disability

For Formiminoglutamic aciduria (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood

Similar variants

FTCD p.Arg255Ter Pathogenic ★★ same condition
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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-glu128lys (accessed [today's date]).

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