Is RINT1 p.Pro185= (c.555G>A) pathogenic?

RINT1 p.Pro185= (c.555G>A) is classified Benign/Likely benign in RINT1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-04-28). Very rare (popmax 0.00883%, sas).

How common is RINT1 p.Pro185= (c.555G>A) in the general population?

RINT1 p.Pro185= (c.555G>A) is very rare (popmax 0.00883%, sas) (gnomAD).

RINT1 p.Pro185=

c.555G>A · rs187674997 · VCV1448115

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00883%, sas)

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 -1.6	GERP -5.8
Overall
CADD	1.371	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00883% South Asian · 8/90,580 alleles

Filtering AF 0.00439% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00314%

Overall 0.0013% 21/1,612,314 alleles · very rare exomes 20/1,460,276 · genomes 1/152,038 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00883%	11,323
Admixed American	0.00168%	59,508
Remaining individualsnot grpmax-eligible	0.0016%	62,408
European (non-Finnish)	0.000933%	107,238

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.Pro185=
Coding: c.555G>A
MANE Select: NM_021930
dbSNP: rs187674997
Type: single nucleotide variant
Location: chr7:105546949 (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.Pro185Ala Uncertain significance ★★ ⚠ same residue
RINT1 p.Pro185Leu Uncertain significance ★★ ⚠ same residue
RINT1 p.Pro185_Glu186insSerAspAspGlnTer Uncertain significance ★ 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-pro185 (accessed [today's date]).

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