Is RINT1 p.Ala138Val (c.413C>T) pathogenic?

RINT1 p.Ala138Val (c.413C>T) is classified Likely benign in RINT1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-10). AlphaMissense: likely benign (0.1594); Ultra-rare (popmax 0.0971%, nfe).

How common is RINT1 p.Ala138Val (c.413C>T) in the general population?

RINT1 p.Ala138Val (c.413C>T) is ultra-rare (popmax 0.0971%, nfe) (gnomAD).

What do computational predictors say about RINT1 p.Ala138Val (c.413C>T)?

AlphaMissense predicts likely benign (score 0.1594) — an in-silico prediction, not a clinical call.

RINT1 p.Ala138Val

c.413C>T · rs150793856 · VCV241408

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1594 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0971%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1594	likely benign
REVEL	0.094	moderately benign-leaning
SaProt	LLR -3.69	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 3.2, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 35 kb · p 0.28 · regional, not allelic
Overall
CADD	18.93	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 0.0971% European (non-Finnish) · 1,146/1,180,030 alleles

Filtering AF 0.0924% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0905%

Overall 0.078% 1,259/1,614,134 alleles · ultra-rare exomes 1,165/1,461,880 · genomes 94/152,254 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0971%	1,030
Remaining individualsnot grpmax-eligible	0.0768%	1,302
Admixed American	0.035%	2,857
South Asian	0.0253%	3,960
African / African-American	0.024%	4,169
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,602
Finnishnot grpmax-eligible	0.00312%	32,011

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.Ala138Val
Coding: c.413C>T
MANE Select: NM_021930
dbSNP: rs150793856
Type: single nucleotide variant
Location: chr7:105542547 (GRCh38)
Gene constraint: LOEUF 0.931 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 85.97

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

Similar variants

RINT1 p.Ala138Thr Uncertain significance ★★ ⚠ same residue
RINT1 p.Ala138Pro Uncertain significance ★ ⚠ same residue
RINT1 p.Ala138= Likely benign ★ same residue
RINT1 c.1107+1G>T Likely pathogenic ★★ same type
RINT1 c.1886+5G>A Uncertain significance ★★ same type
RINT1 c.516-3C>T Uncertain significance ★★ same type
RINT1 c.840-12T>A Uncertain significance ★★ same type
RINT1 c.840-3C>G 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/rint1-p-ala138val (accessed [today's date]).

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