Is FAS p.Cys178Arg (c.532T>C) pathogenic?

FAS p.Cys178Arg (c.532T>C) is classified Pathogenic in FAS (ClinVar, No assertion criteria, 1 submitter; last evaluated 2000-01-01). AlphaMissense: likely pathogenic (0.7348); Absent from gnomAD v4.1; Associated with SQUAMOUS CELL CARCINOMA, BURN SCAR-RELATED, SOMATIC.

What condition is associated with FAS p.Cys178Arg (c.532T>C)?

FAS p.Cys178Arg (c.532T>C) is associated with SQUAMOUS CELL CARCINOMA, BURN SCAR-RELATED, SOMATIC (ClinVar).

How common is FAS p.Cys178Arg (c.532T>C) in the general population?

FAS p.Cys178Arg (c.532T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about FAS p.Cys178Arg (c.532T>C)?

AlphaMissense predicts likely pathogenic (score 0.7348) — an in-silico prediction, not a clinical call.

FAS p.Cys178Arg

c.532T>C · rs121913084 · VCV16512

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7348 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

SQUAMOUS CELL CARCINOMA, BURN SCAR-RELATED, SOMATIC

Computational evidence

Protein change
AlphaMissense	0.7348	likely pathogenic ✓ concordant with ClinVar
REVEL	0.355	indeterminate
SaProt	LLR -9.02	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	Δ0.27	donor gain · deltas
Constraint at this position
Conservation	phyloP -3.5	GERP -2.1
Regional constraint	o/e 0.92	unconstrained · MANE · 23 kb · p 0.16 · regional, not allelic
Overall
CADD	6.573	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

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: FAS
Protein: p.Cys178Arg
Coding: c.532T>C
MANE Select: NM_000043
dbSNP: rs121913084
Type: single nucleotide variant
Location: chr10:89010779 (GRCh38)
Gene constraint: LOEUF 0.372 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 78.21 · 7 PDB
Residue 178: a UniProt-annotated variant site (in squamous cell carcinoma; burn-scar related; somatic mutation); an α-helix

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

Disease context

SQUAMOUS CELL CARCINOMA, BURN SCAR-RELATED, SOMATIC — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

FAS p.Cys178Tyr Uncertain significance ★★ ⚠ same residue
FAS p.Asn118Ser Pathogenic ⚠ same condition
FAS p.Asn255Asp Pathogenic ⚠ same condition
FAS c.196+1G>A Pathogenic/Likely pathogenic ★★ same type
FAS c.443+1G>A Pathogenic/Likely pathogenic ★★ same type
FAS c.651+1G>A Pathogenic/Likely pathogenic ★★ same type
FAS c.651+2T>C Pathogenic ★★ same type
FAS p.Arg250Gln Pathogenic/Likely pathogenic ★★ same type

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/fas-p-cys178arg (accessed [today's date]).

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