Is GSAP p.Ser490Phe (c.1469C>T) pathogenic?

GSAP p.Ser490Phe (c.1469C>T) is classified Uncertain significance in GSAP (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-08). AlphaMissense: likely pathogenic (0.8338); Absent from gnomAD v4.1.

How common is GSAP p.Ser490Phe (c.1469C>T) in the general population?

GSAP p.Ser490Phe (c.1469C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GSAP p.Ser490Phe (c.1469C>T)?

AlphaMissense predicts likely pathogenic (score 0.8338) — an in-silico prediction, not a clinical call.

GSAP p.Ser490Phe

c.1469C>T · rs2535539571 · VCV2324311

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8338 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.8338	likely pathogenic · top 6% in GSAP
REVEL	0.299	indeterminate
SaProt	LLR -8.66	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 4.3, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 105 kb · p 0.86 · regional, not allelic
Overall
CADD	27.1	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: GSAP
Protein: p.Ser490Phe
Coding: c.1469C>T
MANE Select: NM_017439
dbSNP: rs2535539571
Type: single nucleotide variant
Location: chr7:77352966 (GRCh38)
Gene constraint: LOEUF 1.2 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.78

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

Similar variants

GSAP p.Ser490Ala Uncertain significance ★ ⚠ same residue
GSAP p.Pro756Thr Benign ★★ same type
GSAP p.Ala185Val Uncertain significance ★ ⚠ same type
GSAP p.Ala429Thr Uncertain significance ★ ⚠ same type
GSAP p.Ala433Thr Uncertain significance ★ ⚠ same type
GSAP p.Ala457Asp Uncertain significance ★ ⚠ same type
GSAP p.Ala510Ser Uncertain significance ★ ⚠ same type
GSAP p.Ala510Thr Uncertain significance ★ ⚠ 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/gsap-p-ser490phe (accessed [today's date]).

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