Is RINT1 p.Phe668Ser (c.2003T>C) pathogenic?

RINT1 p.Phe668Ser (c.2003T>C) is classified Benign/Likely benign in RINT1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-12-19). AlphaMissense: likely benign (0.0851); Low-frequency (popmax 1.12%, afr).

How common is RINT1 p.Phe668Ser (c.2003T>C) in the general population?

RINT1 p.Phe668Ser (c.2003T>C) is low-frequency (popmax 1.12%, afr) (gnomAD).

What do computational predictors say about RINT1 p.Phe668Ser (c.2003T>C)?

AlphaMissense predicts likely benign (score 0.0851) — an in-silico prediction, not a clinical call.

RINT1 p.Phe668Ser

c.2003T>C · rs35971380 · VCV241401

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.0851 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.12%, afr)

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	0.0851	likely benign
REVEL	0.044	moderately benign-leaning
SaProt	LLR -2.10	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 2.4	GERP 3.2, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 35 kb · p 0.28 · regional, not allelic
Overall
CADD	18.74	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 1.12% African / African-American · 837/75,058 alleles

Filtering AF 1.05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.03%

Overall 0.0553% 892/1,614,146 alleles · low-frequency exomes 458/1,461,862 · genomes 434/152,284 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.12%	90
Remaining individualsnot grpmax-eligible	0.0448%	2,232
Admixed American	0.04%	2,500
European (non-Finnish)	0.000254%	393,337

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.Phe668Ser
Coding: c.2003T>C
MANE Select: NM_021930
dbSNP: rs35971380
Type: single nucleotide variant
Location: chr7:105565393 (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-phe668ser (accessed [today's date]).

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