Is RGR p.Ser241Phe (c.722C>T) pathogenic?

RGR p.Ser241Phe (c.722C>T) is classified Benign/Likely benign in RGR (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-03). AlphaMissense: likely benign (0.1114); Common (popmax 11.2%, eas) — too common for a highly-penetrant pathogenic allele; Associated with inherited retinal dystrophy.

What condition is associated with RGR p.Ser241Phe (c.722C>T)?

RGR p.Ser241Phe (c.722C>T) is associated with inherited retinal dystrophy, retinitis pigmentosa (ClinVar).

What do computational predictors say about RGR p.Ser241Phe (c.722C>T)?

AlphaMissense predicts likely benign (score 0.1114) — an in-silico prediction, not a clinical call.

RGR p.Ser241Phe

Q: How common is RGR p.Ser241Phe (c.722C>T) in the general population?

RGR p.Ser241Phe (c.722C>T) is common (popmax 11.2%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.722C>T · rs61730895 · VCV100573

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.1114 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 11.2%, eas) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

inherited retinal dystrophy

Computational evidence

Protein change
AlphaMissense	0.1114	likely benign
REVEL	0.102	moderately benign-leaning
SaProt	LLR -7.01	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.5	GERP 2.3, phastCons 0.004
Overall
CADD	14.52	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

Grpmax group 11.2% East Asian · 5,024/44,874 alleles

Filtering AF 10.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 10.8%

Overall 4.39% 70,923/1,614,066 alleles · common exomes 64,882/1,461,764 · genomes 6,041/152,302 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	11.2%	9
Admixed American	7.85%	13
South Asian	6.92%	14
Remaining individualsnot grpmax-eligible	4.53%	22
European (non-Finnish)	4.01%	25
Ashkenazi Jewishnot grpmax-eligible	3.67%	27
Finnishnot grpmax-eligible	3.34%	30
Middle Eastern	1.88%	53
African / African-American	1.8%	56
Amishnot grpmax-eligible	0.439%	228

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.Ser241Phe
Coding: c.722C>T
MANE Select: NM_001012720
dbSNP: rs61730895
Type: single nucleotide variant
Location: chr10:84257984 (GRCh38)
Structure: AlphaFold pLDDT 62.88
Residue 241: the ras-gef domain; a UniProt-annotated variant site (in)

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

Disease context

inherited retinal dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: retinitis pigmentosa

Similar variants

RGR p.Ala234Thr Uncertain significance ★★ ⚠ same condition
RGR p.Arg113Cys Uncertain significance ★★ ⚠ same condition
RGR p.Arg289Gln Uncertain significance ★★ ⚠ same condition
RGR p.Arg80His Uncertain significance ★★ ⚠ same condition
RGR p.Asp154Asn Uncertain significance ★★ ⚠ same condition
RGR p.Gly87Ser Uncertain significance ★★ ⚠ same condition
RGR p.Met199Val Uncertain significance ★★ ⚠ same condition
RGR p.Thr37Ile Uncertain significance ★★ ⚠ same condition

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-ser241phe (accessed [today's date]).

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