Is RASGRP1 p.Ser225Pro (c.673T>C) pathogenic?

RASGRP1 p.Ser225Pro (c.673T>C) is classified Uncertain significance in RASGRP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-12). AlphaMissense: ambiguous (0.5329); Absent from gnomAD v4.1.

How common is RASGRP1 p.Ser225Pro (c.673T>C) in the general population?

RASGRP1 p.Ser225Pro (c.673T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about RASGRP1 p.Ser225Pro (c.673T>C)?

AlphaMissense predicts ambiguous (score 0.5329) — an in-silico prediction, not a clinical call.

RASGRP1 p.Ser225Pro

c.673T>C · rs2542912855 · VCV3151849

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5329 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.5329	ambiguous
REVEL	0.332	indeterminate
SaProt	LLR -9.50	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 1.3, phastCons 1
Regional constraint	o/e 0.73	unconstrained · MANE · 63 kb · p 9.6e-13 · regional, not allelic
Overall
CADD	23.8	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: RASGRP1
Protein: p.Ser225Pro
Coding: c.673T>C
MANE Select: NM_005739
dbSNP: rs2542912855
Type: single nucleotide variant
Location: chr15:38516199 (GRCh38)
Gene constraint: LOEUF 0.538 · pLI 0.48 (gnomAD)
Structure: AlphaFold pLDDT 72.43 · 2 PDB
Residue 225: the ras-gef domain

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

Similar variants

RASGRP1 p.Ser225= 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
RASGRP1 p.Arg741His 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-ser225pro (accessed [today's date]).

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