Is RGR p.Ser243= (c.729C>T) pathogenic?

RGR p.Ser243= (c.729C>T) is classified Likely benign in RGR (ClinVar, Single submitter, 1 submitter; last evaluated 2018-05-30). Very rare (popmax 6.2e-05%).

How common is RGR p.Ser243= (c.729C>T) in the general population?

RGR p.Ser243= (c.729C>T) is very rare (popmax 6.2e-05%) (gnomAD).

RGR p.Ser243=

c.729C>T · rs1589337352 · VCV744588

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 6.2e-05%)

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 -0.18	GERP 2.1, phastCons 0.55
Overall
CADD	6.466	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.2e-05%

Overall 6.2e-05% 1/1,614,076 alleles · very rare exomes 1/1,461,766 · genomes 0/152,310 · joint denominator

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: RGR
Protein: p.Ser243=
Coding: c.729C>T
MANE Select: NM_001012720
dbSNP: rs1589337352
Type: single nucleotide variant
Location: chr10:84257991 (GRCh38)
Structure: AlphaFold pLDDT 62.88
Residue 243: the ras-gef domain

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

Similar variants

RGR p.Ser243Phe Uncertain significance ★★ same residue
RGR c.358+1G>A Uncertain significance ★★ same type
RGR p.Ala110Thr Uncertain significance ★★ ⚠ same type
RGR p.Ala186Thr Uncertain significance ★★ ⚠ same type
RGR p.Ala217Gly Uncertain significance ★★ ⚠ same type
RGR p.Ala234Thr Uncertain significance ★★ ⚠ same type
RGR p.Ala251Thr Uncertain significance ★★ ⚠ same type
RGR p.Ala251Val 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/rgr-p-ser243 (accessed [today's date]).

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