Is GP6 p.Ser4Cys (c.11C>G) pathogenic?

GP6 p.Ser4Cys (c.11C>G) is classified Uncertain significance in GP6 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-25). AlphaMissense: likely benign (0.104); Ultra-rare (popmax 0.0491%, sas); Associated with Inborn genetic diseases.

What condition is associated with GP6 p.Ser4Cys (c.11C>G)?

GP6 p.Ser4Cys (c.11C>G) is associated with Inborn genetic diseases (ClinVar).

How common is GP6 p.Ser4Cys (c.11C>G) in the general population?

GP6 p.Ser4Cys (c.11C>G) is ultra-rare (popmax 0.0491%, sas) (gnomAD).

What do computational predictors say about GP6 p.Ser4Cys (c.11C>G)?

AlphaMissense predicts likely benign (score 0.104) — an in-silico prediction, not a clinical call.

GP6 p.Ser4Cys

c.11C>G · VCV3521389

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.104 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0491%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.104	likely benign
REVEL	0.03	moderately benign-leaning
SaProt	LLR -8.70	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 0.06	GERP -3.9
Overall
CADD	12.85	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

Grpmax group 0.0491% South Asian · 43/87,522 alleles

Filtering AF 0.0374% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0334%

Overall 0.00283% 45/1,591,160 alleles · ultra-rare exomes 43/1,439,000 · genomes 2/152,160 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0491%	2,035
Remaining individualsnot grpmax-eligible	0.00324%	30,821

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: GP6
Protein: p.Ser4Cys
Coding: c.11C>G
MANE Select: NM_016363
Type: single nucleotide variant
Location: chr19:55038226 (GRCh38)
Gene constraint: LOEUF 1.734 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 76.52 · 6 PDB

Full GP6 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

GP6 c.*106A>C Uncertain significance ★★ same condition
GP6 c.*189C>T Uncertain significance ★★ same condition
GP6 c.*304C>T Uncertain significance ★★ same condition
GP6 c.*523G>C Uncertain significance ★★ same condition
GP6 c.*531T>C Uncertain significance ★★ same condition
GP6 p.Arg262Cys Uncertain significance ★★ ⚠ same condition
GP6 p.Arg299Trp Uncertain significance ★★ ⚠ same condition
GP6 p.Arg319Trp 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/gp6-p-ser4cys (accessed [today's date]).

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