Is RINT1 p.Phe674Ser (c.2021T>C) pathogenic?

RINT1 p.Phe674Ser (c.2021T>C) is classified Conflicting classifications of pathogenicity in RINT1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-10-12). AlphaMissense: likely benign (0.1497); Very rare (popmax 0.005%, amr).

How common is RINT1 p.Phe674Ser (c.2021T>C) in the general population?

RINT1 p.Phe674Ser (c.2021T>C) is very rare (popmax 0.005%, amr) (gnomAD).

What do computational predictors say about RINT1 p.Phe674Ser (c.2021T>C)?

AlphaMissense predicts likely benign (score 0.1497) — an in-silico prediction, not a clinical call.

RINT1 p.Phe674Ser

c.2021T>C · rs757668486 · VCV1500720

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1497 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

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	0.1497	likely benign
REVEL	0.106	moderately benign-leaning
SaProt	LLR -7.21	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 1.2	GERP 2.1, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 35 kb · p 0.28 · regional, not allelic
Overall
CADD	19.92	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 0.005% Admixed American · 3/59,998 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.000558% 9/1,614,112 alleles · very rare exomes 7/1,461,882 · genomes 2/152,230 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	19,999
European (non-Finnish)	0.000508%	196,675

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.Phe674Ser
Coding: c.2021T>C
MANE Select: NM_021930
dbSNP: rs757668486
Type: single nucleotide variant
Location: chr7:105565411 (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-phe674ser (accessed [today's date]).

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