Is RASGRP1 p.Ser210= (c.630C>T) pathogenic?

RASGRP1 p.Ser210= (c.630C>T) is classified Likely benign in RASGRP1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-07). Ultra-rare (popmax 0.0117%, amr).

How common is RASGRP1 p.Ser210= (c.630C>T) in the general population?

RASGRP1 p.Ser210= (c.630C>T) is ultra-rare (popmax 0.0117%, amr) (gnomAD).

RASGRP1 p.Ser210=

c.630C>T · rs373809590 · VCV1576769

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0117%, amr)

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 -14	GERP -5
Overall
CADD	0.242	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0117% Admixed American · 7/59,950 alleles

Filtering AF 0.00544% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00381%

Overall 0.00424% 68/1,602,220 alleles · ultra-rare exomes 61/1,450,126 · genomes 7/152,094 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0172%	5,819
Admixed Americangrpmax	0.0117%	8,564
Remaining individualsnot grpmax-eligible	0.00483%	20,707
European (non-Finnish)	0.00368%	27,195
South Asian	0.0033%	30,275
East Asian	0.00223%	44,822

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser210=
Coding: c.630C>T
MANE Select: NM_005739
dbSNP: rs373809590
Type: single nucleotide variant
Location: chr15:38516242 (GRCh38)
Gene constraint: LOEUF 0.538 · pLI 0.48 (gnomAD)
Structure: AlphaFold pLDDT 72.43 · 2 PDB
Residue 210: the ras-gef domain; an α-helix

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

Similar variants

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
RASGRP1 p.Asn241Ser 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-ser210 (accessed [today's date]).

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