Is OCRL p.Ala117Val (c.350C>T) pathogenic?

OCRL p.Ala117Val (c.350C>T) is classified Uncertain significance in OCRL (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-16). AlphaMissense: likely benign (0.0845); Ultra-rare (popmax 0.0233%, mid); Associated with oculocerebrorenal syndrome.

What condition is associated with OCRL p.Ala117Val (c.350C>T)?

OCRL p.Ala117Val (c.350C>T) is associated with oculocerebrorenal syndrome (ClinVar).

How common is OCRL p.Ala117Val (c.350C>T) in the general population?

OCRL p.Ala117Val (c.350C>T) is ultra-rare (popmax 0.0233%, mid) (gnomAD).

What do computational predictors say about OCRL p.Ala117Val (c.350C>T)?

AlphaMissense predicts likely benign (score 0.0845) — an in-silico prediction, not a clinical call.

OCRL p.Ala117Val

c.350C>T · VCV4702071

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0845 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0233%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

oculocerebrorenal syndrome

Computational evidence

Protein change
AlphaMissense	0.0845	likely benign
REVEL	0.354	indeterminate
SaProt	LLR -6.35	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.23 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 19 kb · p 0.85 · regional, not allelic
Overall
CADD	21.4	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 0.0233% Middle Eastern · 1/4,283 alleles

Filtering AF 0.00173% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000879%

Overall 0.000423% 5/1,182,788 alleles · ultra-rare exomes 5/1,068,901 · genomes 0/113,887 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0233%	4,283
Admixed American	0.00652%	15,345
European (non-Finnish)	0.000115%	868,863

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.Ala117Val
Coding: c.350C>T
MANE Select: NM_000276
Type: single nucleotide variant
Location: chrX:129557861 (GRCh38)
Structure: AlphaFold pLDDT 82.91 · 5 PDB
Residue 117: the ph domain; an α-helix

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

Disease context

oculocerebrorenal syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

OCRL p.Ala117= Likely benign ★★ same residue
OCRL c.1244+1G>A Pathogenic/Likely pathogenic ★★ same condition
OCRL c.1714-1G>A Pathogenic ★★ same condition
OCRL c.2256+1G>T Likely pathogenic ★★ same condition
OCRL c.560+1G>C Pathogenic/Likely pathogenic ★★ same condition
OCRL c.940-11G>A Pathogenic/Likely pathogenic ★★ same condition
OCRL p.Ala861Thr Pathogenic/Likely pathogenic ★★ ⚠ same condition
OCRL p.Arg318Cys Pathogenic/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-ala117val (accessed [today's date]).

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