Is RINT1 p.Asp552= (c.1656T>C) pathogenic?

RINT1 p.Asp552= (c.1656T>C) is classified Benign/Likely benign in RINT1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-14). Rare (popmax 0.805%, eas).

How common is RINT1 p.Asp552= (c.1656T>C) in the general population?

RINT1 p.Asp552= (c.1656T>C) is rare (popmax 0.805%, eas) (gnomAD).

RINT1 p.Asp552=

c.1656T>C · rs192297021 · VCV416401

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.805%, eas)

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 -4.6	GERP -3.5
Overall
CADD	2.954	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.805% East Asian · 361/44,840 alleles

Filtering AF 0.737% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.71%

Overall 0.0242% 390/1,613,418 alleles · rare exomes 370/1,461,072 · genomes 20/152,346 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.805%	124
Middle Eastern	0.0165%	6,060
Remaining individualsnot grpmax-eligible	0.016%	6,248
South Asian	0.0033%	30,333
Admixed American	0.00167%	59,904
European (non-Finnish)	0.00119%	84,259

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.Asp552=
Coding: c.1656T>C
MANE Select: NM_021930
dbSNP: rs192297021
Type: single nucleotide variant
Location: chr7:105555212 (GRCh38)
Gene constraint: LOEUF 0.931 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 85.97
Residue 552: the rint1/tip20 domain

Full RINT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

RINT1 p.Asp552His 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
RINT1 p.Ala138Thr Uncertain significance ★★ ⚠ same type
RINT1 p.Ala13Val 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-asp552 (accessed [today's date]).

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