Is OCRL p.Pro871Thr (c.2611C>A) pathogenic?

OCRL p.Pro871Thr (c.2611C>A) is classified Uncertain significance in OCRL (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-29). AlphaMissense: ambiguous (0.5027); Absent from gnomAD v4.1; Associated with OCRL-related disorder.

What condition is associated with OCRL p.Pro871Thr (c.2611C>A)?

OCRL p.Pro871Thr (c.2611C>A) is associated with OCRL-related disorder (ClinVar).

How common is OCRL p.Pro871Thr (c.2611C>A) in the general population?

OCRL p.Pro871Thr (c.2611C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about OCRL p.Pro871Thr (c.2611C>A)?

AlphaMissense predicts ambiguous (score 0.5027) — an in-silico prediction, not a clinical call.

OCRL p.Pro871Thr

c.2611C>A · rs2521951274 · VCV2629585

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5027 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

OCRL-related disorder

Computational evidence

Protein change
AlphaMissense	0.5027	ambiguous
REVEL	0.224	benign-leaning
SaProt	LLR -10.89	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	phastCons 1
Regional constraint	o/e 0.54	unconstrained · MANE · 31 kb · p 4.7e-26 · regional, not allelic
Overall
CADD	24.3	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.Pro871Thr
Coding: c.2611C>A
MANE Select: NM_000276
dbSNP: rs2521951274
Type: single nucleotide variant
Location: chrX:129590175 (GRCh38)
Structure: AlphaFold pLDDT 82.91 · 5 PDB
Residue 871: the rho-gap domain

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

Disease context

OCRL-related disorder

Similar variants

OCRL p.Pro871= Likely benign ★ same residue
OCRL p.Arg334Ter Pathogenic ★★ same condition
OCRL p.Arg500Gln Pathogenic ★★ same condition
OCRL p.Arg663Ter Pathogenic ★★ same condition
OCRL p.Arg695Ter Pathogenic/Likely pathogenic ★★ same condition
OCRL c.120-2A>G Likely pathogenic ★ same condition
OCRL p.Arg318Leu Likely pathogenic ★ same condition
OCRL p.Asp451Gly Likely pathogenic ★ ⚠ 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/ocrl-p-pro871thr (accessed [today's date]).

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