Is FTCD p.Tyr495Phe (c.1484A>T) pathogenic?

FTCD p.Tyr495Phe (c.1484A>T) is classified Uncertain significance in FTCD (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-06-19). AlphaMissense: likely benign (0.1756); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with FTCD p.Tyr495Phe (c.1484A>T)?

FTCD p.Tyr495Phe (c.1484A>T) is associated with Inborn genetic diseases (ClinVar).

How common is FTCD p.Tyr495Phe (c.1484A>T) in the general population?

FTCD p.Tyr495Phe (c.1484A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about FTCD p.Tyr495Phe (c.1484A>T)?

AlphaMissense predicts likely benign (score 0.1756) — an in-silico prediction, not a clinical call.

FTCD p.Tyr495Phe

c.1484A>T · rs1489442504 · VCV2442735

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1756 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1756	likely benign
REVEL	0.228	benign-leaning
SaProt	LLR -8.48	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 7.4	GERP 1.2, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 19 kb · p 0.00063 · regional, not allelic
Overall
CADD	23.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: FTCD
Protein: p.Tyr495Phe
Coding: c.1484A>T
MANE Select: NM_206965
dbSNP: rs1489442504
Type: single nucleotide variant
Location: chr21:46137294 (GRCh38)
Gene constraint: LOEUF 1.61 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 95.30
Residue 495: 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-tyr495phe (accessed [today's date]).

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