Is RIN1 p.Gln511Pro (c.1532A>C) pathogenic?

RIN1 p.Gln511Pro (c.1532A>C) is classified Uncertain significance in RIN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-03). AlphaMissense: ambiguous (0.5542); Very rare (popmax 0.000954%, nfe).

How common is RIN1 p.Gln511Pro (c.1532A>C) in the general population?

RIN1 p.Gln511Pro (c.1532A>C) is very rare (popmax 0.000954%, nfe) (gnomAD).

What do computational predictors say about RIN1 p.Gln511Pro (c.1532A>C)?

AlphaMissense predicts ambiguous (score 0.5542) — an in-silico prediction, not a clinical call.

RIN1 p.Gln511Pro

c.1532A>C · VCV4578140

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5542 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000954%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.5542	ambiguous
REVEL	0.264	benign-leaning
SaProt	LLR -11.95	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	GERP 1.7, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 4,123 bp · p 0.45 · regional, not allelic
Overall
CADD	25.6	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 0.000954% European (non-Finnish) · 11/1,153,254 alleles

Filtering AF 0.000512% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000374%

Overall 0.000769% 12/1,561,048 alleles · very rare exomes 11/1,408,936 · genomes 1/152,112 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00165%	60,500
European (non-Finnish)grpmax	0.000954%	104,841

Remaining individuals 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: RIN1
Protein: p.Gln511Pro
Coding: c.1532A>C
MANE Select: NM_004292
Type: single nucleotide variant
Location: chr11:66333978 (GRCh38)
Gene constraint: LOEUF 1.22 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.78
Residue 511: the vps9 domain; the 'ras and 14-3-3 protein binding region' region

Full RIN1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

RIN1 p.Ala690= Benign ★★ same type
RIN1 p.Gly737= Benign ★★ same type
RIN1 p.Thr643= Benign/Likely benign ★★ same type
RIN1 p.Val700Ile Benign ★★ same type
RIN1 p.Ala111Thr Uncertain significance ★ ⚠ same type
RIN1 p.Ala168Thr Uncertain significance ★ ⚠ same type
RIN1 p.Ala221Ser Uncertain significance ★ ⚠ same type
RIN1 p.Ala31Val Uncertain significance ★ ⚠ 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/rin1-p-gln511pro (accessed [today's date]).

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