Is GSC p.Ala63= (c.189C>T) pathogenic?

GSC p.Ala63= (c.189C>T) is classified Likely benign in GSC (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-21). Ultra-rare (popmax 0.0411%, amr).

How common is GSC p.Ala63= (c.189C>T) in the general population?

GSC p.Ala63= (c.189C>T) is ultra-rare (popmax 0.0411%, amr) (gnomAD).

GSC p.Ala63=

c.189C>T · rs936564254 · VCV2186692

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0411%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.3	GERP 1.3, phastCons 1
Overall
CADD	15.37	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0411% Admixed American · 12/29,180 alleles

Filtering AF 0.0237% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0186%

Overall 0.0019% 27/1,419,668 alleles · ultra-rare exomes 19/1,267,634 · genomes 8/152,034 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0411%	2,432
Remaining individualsnot grpmax-eligible	0.00734%	13,617
South Asian	0.00455%	21,996
European (non-Finnish)	0.000728%	137,451

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: GSC
Protein: p.Ala63=
Coding: c.189C>T
MANE Select: NM_173849
dbSNP: rs936564254
Type: single nucleotide variant
Location: chr14:94769827 (GRCh38)
Gene constraint: LOEUF 1.398 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.68 · 1 PDB

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

Similar variants

GSC p.Ala63Gly Uncertain significance ★ ⚠ same residue
GSC p.Ala63Val Uncertain significance ★ ⚠ same residue
GSC p.Ala26Val Uncertain significance ★★ ⚠ same type
GSC p.Ala30Val Uncertain significance ★★ ⚠ same type
GSC p.Lys183Gln Uncertain significance ★★ ⚠ same type
GSC p.Tyr54Ser Uncertain significance ★★ ⚠ same type
GSC c.356-186C>T Benign ★★ same type
GSC p.Ala72Thr Benign ★★ 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/gsc-p-ala63 (accessed [today's date]).

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