Is OCRL p.Ala395Val (c.1184C>T) pathogenic?

OCRL p.Ala395Val (c.1184C>T) is classified Likely benign in OCRL (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-10-18). AlphaMissense: likely benign (0.2443); Ultra-rare (popmax 0.023%, nfe); Associated with Nephrolithiasis/nephrocalcinosis.

What condition is associated with OCRL p.Ala395Val (c.1184C>T)?

OCRL p.Ala395Val (c.1184C>T) is associated with Nephrolithiasis/nephrocalcinosis, oculocerebrorenal syndrome (ClinVar).

How common is OCRL p.Ala395Val (c.1184C>T) in the general population?

OCRL p.Ala395Val (c.1184C>T) is ultra-rare (popmax 0.023%, nfe) (gnomAD).

What do computational predictors say about OCRL p.Ala395Val (c.1184C>T)?

AlphaMissense predicts likely benign (score 0.2443) — an in-silico prediction, not a clinical call.

OCRL p.Ala395Val

c.1184C>T · rs145139567 · VCV1149743

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2443 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.023%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Nephrolithiasis/nephrocalcinosis

Computational evidence

Protein change
AlphaMissense	0.2443	likely benign
REVEL	0.763	pathogenic-leaning
SaProt	LLR -6.53	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.9, phastCons 1
Regional constraint	o/e 0.54	unconstrained · MANE · 31 kb · p 4.7e-26 · regional, not allelic
Overall
CADD	25.2	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

Grpmax group 0.023% European (non-Finnish) · 206/894,925 alleles

Filtering AF 0.0204% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0194%

Overall 0.0185% 224/1,209,451 alleles · ultra-rare exomes 211/1,097,849 · genomes 13/111,602 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0545%	1,835
European (non-Finnish)grpmax	0.023%	4,344
Remaining individualsnot grpmax-eligible	0.0105%	9,516
Finnishnot grpmax-eligible	0.00215%	46,518

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ala395Val
Coding: c.1184C>T
MANE Select: NM_000276
dbSNP: rs145139567
Type: single nucleotide variant
Location: chrX:129562726 (GRCh38)
Structure: AlphaFold pLDDT 82.91 · 5 PDB
Residue 395: the 5-ppase domain; an α-helix

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

Disease context

Nephrolithiasis/nephrocalcinosis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: oculocerebrorenal syndrome

Similar variants

OCRL p.Ala395= 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-ala395val (accessed [today's date]).

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