Is RASGRP1 p.Arg265= (c.795C>T) pathogenic?

RASGRP1 p.Arg265= (c.795C>T) is classified Likely benign in RASGRP1 (ClinVar, Single submitter, 2 submitters; last evaluated 2026-01-06). Ultra-rare (popmax 0.087%, eas).

How common is RASGRP1 p.Arg265= (c.795C>T) in the general population?

RASGRP1 p.Arg265= (c.795C>T) is ultra-rare (popmax 0.087%, eas) (gnomAD).

RASGRP1 p.Arg265=

c.795C>T · rs572243858 · VCV2195030

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.087%, 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 -0.057	GERP -1.5, phastCons 0.091
Overall
CADD	7.995	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.087% East Asian · 39/44,832 alleles

Filtering AF 0.0653% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0578%

Overall 0.00328% 53/1,613,726 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.087%	1,150
South Asian	0.011%	9,108
Remaining individualsnot grpmax-eligible	0.0064%	15,616

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: RASGRP1
Protein: p.Arg265=
Coding: c.795C>T
MANE Select: NM_005739
dbSNP: rs572243858
Type: single nucleotide variant
Location: chr15:38512837 (GRCh38)
Gene constraint: LOEUF 0.538 · pLI 0.48 (gnomAD)
Structure: AlphaFold pLDDT 72.43 · 2 PDB
Residue 265: the ras-gef domain; a UniProt-annotated variant site (in imd64; loss of protein expression); a UniProt-annotated variant site (in imd64)

Full RASGRP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

RASGRP1 p.Arg265Cys Uncertain significance ★ ⚠ same residue
RASGRP1 p.Arg265His Uncertain significance ★ ⚠ same residue
RASGRP1 c.327-1C>G Pathogenic/Likely pathogenic ★★ same type
RASGRP1 p.Arg81Ter Pathogenic/Likely pathogenic ★★ same type
RASGRP1 p.Ala57Ser Uncertain significance ★★ ⚠ same type
RASGRP1 p.Arg167Cys Uncertain significance ★★ ⚠ same type
RASGRP1 p.Arg177His Uncertain significance ★★ ⚠ same type
RASGRP1 p.Arg663Gln 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/rasgrp1-p-arg265 (accessed [today's date]).

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