Is RINT1 p.Arg656Gln (c.1967G>A) pathogenic?

RINT1 p.Arg656Gln (c.1967G>A) is classified Uncertain significance in RINT1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-08). AlphaMissense: likely benign (0.3057); Very rare (popmax 0.00223%, eas).

How common is RINT1 p.Arg656Gln (c.1967G>A) in the general population?

RINT1 p.Arg656Gln (c.1967G>A) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about RINT1 p.Arg656Gln (c.1967G>A)?

AlphaMissense predicts likely benign (score 0.3057) — an in-silico prediction, not a clinical call.

RINT1 p.Arg656Gln

c.1967G>A · rs746864752 · VCV1051054

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.3057 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.3057	likely benign
REVEL	0.211	benign-leaning
SaProt	LLR -6.22	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 8.5	GERP 3.2, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 35 kb · p 0.28 · regional, not allelic
Overall
CADD	25.4	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 0.00223% East Asian · 1/44,896 alleles

Filtering AF 0.000763% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000605%

Overall 0.00118% 19/1,614,048 alleles · very rare exomes 18/1,461,864 · genomes 1/152,184 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,896
Remaining individualsnot grpmax-eligible	0.0016%	62,488
Finnishnot grpmax-eligible	0.00156%	64,024
European (non-Finnish)	0.00127%	78,669
South Asian	0.0011%	91,092

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: RINT1
Protein: p.Arg656Gln
Coding: c.1967G>A
MANE Select: NM_021930
dbSNP: rs746864752
Type: single nucleotide variant
Location: chr7:105565357 (GRCh38)

Full RINT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/rint1-p-arg656gln (accessed [today's date]).

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