Is FTCD p.Met373Val (c.1117A>G) pathogenic?

FTCD p.Met373Val (c.1117A>G) is classified Uncertain significance in FTCD (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-10). AlphaMissense: ambiguous (0.3625); Very rare (popmax 0.00197%, amr); Associated with Inborn genetic diseases.

What condition is associated with FTCD p.Met373Val (c.1117A>G)?

FTCD p.Met373Val (c.1117A>G) is associated with Inborn genetic diseases (ClinVar).

How common is FTCD p.Met373Val (c.1117A>G) in the general population?

FTCD p.Met373Val (c.1117A>G) is very rare (popmax 0.00197%, amr) (gnomAD).

What do computational predictors say about FTCD p.Met373Val (c.1117A>G)?

AlphaMissense predicts ambiguous (score 0.3625) — an in-silico prediction, not a clinical call.

FTCD p.Met373Val

c.1117A>G · VCV3852063

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3625 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00197%, amr)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3625	ambiguous
REVEL	0.671	pathogenic-leaning
SaProt	LLR -10.66	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.3	GERP 1.4, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 19 kb · p 0.00063 · regional, not allelic
Overall
CADD	25.0	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 0.00197% Admixed American · 1/50,864 alleles

Overall 0.00013% 2/1,544,094 alleles · very rare exomes 2/1,392,162 · genomes 0/151,932 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00197%	50,864
South Asian	0.00119%	83,896

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.Met373Val
Coding: c.1117A>G
MANE Select: NM_206965
Type: single nucleotide variant
Location: chr21:46145560 (GRCh38)
Gene constraint: LOEUF 1.61 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 95.30
Residue 373: the 'cyclodeaminase/cyclohydrolase' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

FTCD p.Arg255Ter Pathogenic ★★ same condition
FTCD p.Ala108Thr Uncertain significance ★★ ⚠ same condition
FTCD p.Ala159Val Uncertain significance ★★ ⚠ same condition
FTCD p.Ala352Val Uncertain significance ★★ ⚠ same condition
FTCD p.Ala361Val Uncertain significance ★★ same condition
FTCD p.Ala418Thr Uncertain significance ★★ ⚠ same condition
FTCD p.Ala455Thr Uncertain significance ★★ ⚠ same condition
FTCD p.Ala455Val 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-met373val (accessed [today's date]).

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