Is GP6 p.Pro24Leu (c.71C>T) pathogenic?

GP6 p.Pro24Leu (c.71C>T) is classified Uncertain significance in GP6 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-24). AlphaMissense: likely benign (0.0782); Ultra-rare (popmax 0.0661%, mid); Associated with Inborn genetic diseases.

What condition is associated with GP6 p.Pro24Leu (c.71C>T)?

GP6 p.Pro24Leu (c.71C>T) is associated with Inborn genetic diseases (ClinVar).

How common is GP6 p.Pro24Leu (c.71C>T) in the general population?

GP6 p.Pro24Leu (c.71C>T) is ultra-rare (popmax 0.0661%, mid) (gnomAD).

What do computational predictors say about GP6 p.Pro24Leu (c.71C>T)?

AlphaMissense predicts likely benign (score 0.0782) — an in-silico prediction, not a clinical call.

GP6 p.Pro24Leu

c.71C>T · rs767523302 · VCV1915782

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0782 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0661%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0782	likely benign
REVEL	0.054	moderately benign-leaning
SaProt	LLR -5.17	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.54 · evaluated, not missing
Constraint at this position
Conservation	phyloP -4.6	GERP -4
Overall
CADD	5.832	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 0.0661% Middle Eastern · 4/6,052 alleles

Filtering AF 0.0226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0135%

Overall 0.00322% 52/1,612,554 alleles · ultra-rare exomes 46/1,460,220 · genomes 6/152,334 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0661%	1,513
East Asian	0.0156%	6,405
Remaining individualsnot grpmax-eligible	0.00641%	15,603
African / African-American	0.004%	25,015
Admixed American	0.00334%	29,938
European (non-Finnish)	0.00263%	38,039
South Asian	0.0011%	90,918

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.Pro24Leu
Coding: c.71C>T
MANE Select: NM_016363
dbSNP: rs767523302
Type: single nucleotide variant
Location: chr19:55032393 (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 p.Pro24= Likely benign ★ same residue
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

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-pro24leu (accessed [today's date]).

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