Is OCRL p.Ala309Val (c.926C>T) pathogenic?

OCRL p.Ala309Val (c.926C>T) is classified Uncertain significance in OCRL (ClinVar, Single submitter, 1 submitter; last evaluated 2017-02-01). AlphaMissense: likely benign (0.2373); Very rare (popmax 0.000116%, nfe).

How common is OCRL p.Ala309Val (c.926C>T) in the general population?

OCRL p.Ala309Val (c.926C>T) is very rare (popmax 0.000116%, nfe) (gnomAD).

What do computational predictors say about OCRL p.Ala309Val (c.926C>T)?

AlphaMissense predicts likely benign (score 0.2373) — an in-silico prediction, not a clinical call.

OCRL p.Ala309Val

c.926C>T · rs1057524866 · VCV393270

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2373 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000116%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.2373	likely benign
REVEL	0.411	indeterminate
SaProt	LLR -7.24	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.7	GERP 1, phastCons 1
Regional constraint	o/e 0.54	unconstrained · MANE · 31 kb · p 4.7e-26 · regional, not allelic
Overall
CADD	22.6	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 0.000116% European (non-Finnish) · 1/861,472 alleles

Overall 8.52e-05% 1/1,174,127 alleles · very rare exomes 1/1,060,907 · genomes 0/113,220 · joint denominator

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: OCRL
Protein: p.Ala309Val
Coding: c.926C>T
MANE Select: NM_000276
dbSNP: rs1057524866
Type: single nucleotide variant
Location: chrX:129561280 (GRCh38)
Structure: AlphaFold pLDDT 82.91 · 5 PDB
Residue 309: the 5-ppase domain

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

Similar variants

OCRL c.1244+1G>A Pathogenic/Likely pathogenic ★★ same type
OCRL c.1714-1G>A Pathogenic ★★ same type
OCRL c.2256+1G>T Likely pathogenic ★★ same type
OCRL c.560+1G>C Pathogenic/Likely pathogenic ★★ same type
OCRL c.940-11G>A Pathogenic/Likely pathogenic ★★ same type
OCRL p.Ala861Thr Pathogenic/Likely pathogenic ★★ ⚠ same type
OCRL p.Arg318Cys Pathogenic/Likely pathogenic ★★ same type
OCRL p.Arg318His 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/ocrl-p-ala309val (accessed [today's date]).

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