Is RIN1 p.Phe116= (c.348C>T) pathogenic?

RIN1 p.Phe116= (c.348C>T) is classified Likely benign in RIN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-01). Ultra-rare (popmax 0.0165%, mid).

How common is RIN1 p.Phe116= (c.348C>T) in the general population?

RIN1 p.Phe116= (c.348C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

RIN1 p.Phe116=

c.348C>T · rs760724156 · VCV2641987

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.078	GERP -0.85, phastCons 0.51
Overall
CADD	12.79	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,066 alleles

Filtering AF 0.000616% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000475%

Overall 0.00118% 19/1,610,822 alleles · ultra-rare exomes 17/1,458,620 · genomes 2/152,202 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,066
Remaining individualsnot grpmax-eligible	0.00321%	31,144
South Asian	0.0022%	45,443
African / African-American	0.00134%	74,864
European (non-Finnish)	0.0011%	90,607

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: RIN1
Protein: p.Phe116=
Coding: c.348C>T
MANE Select: NM_004292
dbSNP: rs760724156
Type: single nucleotide variant
Location: chr11:66335796 (GRCh38)
Gene constraint: LOEUF 1.22 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.78
Residue 116: the sh2 domain

Full RIN1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

RIN1 p.Ala690= Benign ★★ same type
RIN1 p.Gly737= Benign ★★ same type
RIN1 p.Thr643= Benign/Likely benign ★★ same type
RIN1 p.Val700Ile Benign ★★ same type
RIN1 p.Ala111Thr Uncertain significance ★ ⚠ same type
RIN1 p.Ala168Thr Uncertain significance ★ ⚠ same type
RIN1 p.Ala221Ser Uncertain significance ★ ⚠ same type
RIN1 p.Ala31Val 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/rin1-p-phe116 (accessed [today's date]).

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