Is OCRL p.Phe894Val (c.2680T>G) pathogenic?

OCRL p.Phe894Val (c.2680T>G) is classified Uncertain significance in OCRL (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-31). AlphaMissense: likely pathogenic (0.8543); Absent from gnomAD v4.1.

How common is OCRL p.Phe894Val (c.2680T>G) in the general population?

OCRL p.Phe894Val (c.2680T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about OCRL p.Phe894Val (c.2680T>G)?

AlphaMissense predicts likely pathogenic (score 0.8543) — an in-silico prediction, not a clinical call.

OCRL p.Phe894Val

c.2680T>G · rs147629352 · VCV2637577

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8543 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8543	likely pathogenic
REVEL	0.89	moderately pathogenic-leaning
SaProt	LLR -8.67	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.3	phastCons 1
Regional constraint	o/e 0.54	unconstrained · MANE · 31 kb · p 4.7e-26 · regional, not allelic
Overall
CADD	23.7	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: OCRL
Protein: p.Phe894Val
Coding: c.2680T>G
MANE Select: NM_000276
dbSNP: rs147629352
Type: single nucleotide variant
Location: chrX:129590244 (GRCh38)
Structure: AlphaFold pLDDT 82.91 · 5 PDB
Residue 894: an α-helix; the rho-gap domain

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

Similar variants

OCRL p.Phe894Ile Conflicting classifications of pathogenicity ★ ⚠ same residue
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

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-phe894val (accessed [today's date]).

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