Is RINT1 p.Arg656Ter (c.1966C>T) pathogenic?

RINT1 p.Arg656Ter (c.1966C>T) is classified Conflicting classifications of pathogenicity in RINT1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-03-12). Very rare (popmax 0.00668%, eas).

How common is RINT1 p.Arg656Ter (c.1966C>T) in the general population?

RINT1 p.Arg656Ter (c.1966C>T) is very rare (popmax 0.00668%, eas) (gnomAD).

RINT1 p.Arg656Ter

c.1966C>T · rs780062646 · VCV1004811

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00668%, eas)

⚠ 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
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.14	GERP 2.2, phastCons 0.029
Overall
CADD	37.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00668% East Asian · 3/44,880 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.000929% 15/1,614,168 alleles · very rare exomes 15/1,461,866 · genomes 0/152,302 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00668%	14,960
Remaining individualsnot grpmax-eligible	0.0016%	62,508
African / African-American	0.00133%	75,038
South Asian	0.0011%	91,082
European (non-Finnish)	0.000763%	131,114

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.Arg656Ter
Coding: c.1966C>T
MANE Select: NM_021930
dbSNP: rs780062646
Type: single nucleotide variant
Location: chr7:105565356 (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-arg656ter (accessed [today's date]).

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