Is FTCD p.Pro92Ser (c.274C>T) pathogenic?

FTCD p.Pro92Ser (c.274C>T) is classified Uncertain significance in FTCD (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-09-11). AlphaMissense: likely pathogenic (0.8915); Very rare (popmax 0.00783%, amr); Associated with Inborn genetic diseases.

What condition is associated with FTCD p.Pro92Ser (c.274C>T)?

FTCD p.Pro92Ser (c.274C>T) is associated with Inborn genetic diseases, formiminoglutamic aciduria (ClinVar).

How common is FTCD p.Pro92Ser (c.274C>T) in the general population?

FTCD p.Pro92Ser (c.274C>T) is very rare (popmax 0.00783%, amr) (gnomAD).

What do computational predictors say about FTCD p.Pro92Ser (c.274C>T)?

AlphaMissense predicts likely pathogenic (score 0.8915) — an in-silico prediction, not a clinical call.

FTCD p.Pro92Ser

c.274C>T · rs749149640 · VCV282695

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.8915 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00783%, amr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8915	likely pathogenic · top 9% in FTCD
REVEL	0.917	moderately pathogenic-leaning
SaProt	LLR -14.53	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.4, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 19 kb · p 0.00063 · regional, not allelic
Overall
CADD	28.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00783% Admixed American · 4/51,068 alleles

Filtering AF 0.00263% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00153%

Overall 0.00058% 9/1,550,814 alleles · very rare exomes 8/1,398,600 · genomes 1/152,214 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00783%	12,767
East Asian	0.00243%	41,120
African / African-American	0.00137%	73,220
South Asian	0.00119%	84,192
European (non-Finnish)	0.000174%	573,668

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.Pro92Ser
Coding: c.274C>T
MANE Select: NM_206965
dbSNP: rs749149640
Type: single nucleotide variant
Location: chr21:46153000 (GRCh38)
Gene constraint: LOEUF 1.61 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 95.30
Residue 92: the 'formiminotransferase n-subdomain' 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

Also linked: formiminoglutamic aciduria

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.Ala352Val Uncertain significance ★★ ⚠ same condition
FTCD p.Ala361Val 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-pro92ser (accessed [today's date]).

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