Is ROM1 p.Arg223= (c.669G>C) pathogenic?

ROM1 p.Arg223= (c.669G>C) is classified Benign in ROM1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-04). Common (popmax 36.1%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with inherited retinal dystrophy.

What condition is associated with ROM1 p.Arg223= (c.669G>C)?

ROM1 p.Arg223= (c.669G>C) is associated with inherited retinal dystrophy, retinitis pigmentosa (ClinVar).

ROM1 p.Arg223=

Q: How common is ROM1 p.Arg223= (c.669G>C) in the general population?

ROM1 p.Arg223= (c.669G>C) is common (popmax 36.1%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.669G>C · rs1801144 · VCV305166

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 36.1%, nfe) — too common for a highly-penetrant pathogenic allele

Conditions

inherited retinal dystrophy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.392	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP 0.5, phastCons 1
Overall
CADD	8.638	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 36.1% European (non-Finnish) · 426,133/1,179,632 alleles

Filtering AF 36% ClinGen BA1/BS1 input FAF95, joint · FAF99 36%

Overall 32.1% 518,480/1,613,350 alleles · common exomes 478,960/1,461,600 · genomes 39,520/151,750 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	40.3%	2
European (non-Finnish)grpmax	36.1%	3
Remaining individualsnot grpmax-eligible	30.5%	3
Middle Eastern	29.9%	3
Amishnot grpmax-eligible	27.6%	4
Finnishnot grpmax-eligible	23.7%	4
South Asian	22.7%	4
Admixed American	16.9%	6
African / African-American	14.7%	7
East Asian	5.17%	19

Ashkenazi Jewish 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: ROM1
Protein: p.Arg223=
Coding: c.669G>C
MANE Select: NM_000327
dbSNP: rs1801144
Type: single nucleotide variant
Location: chr11:62614336 (GRCh38)
Gene constraint: LOEUF 1.003 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.56 · 1 PDB

Full ROM1 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

ROM1 p.Arg223Trp Uncertain significance ★★ ⚠ same residue
ROM1 p.Arg223Gln Uncertain significance ★★ ⚠ same residue
ROM1 p.Ala265Thr Uncertain significance ★★ ⚠ same condition
ROM1 p.Ala329Val Uncertain significance ★★ ⚠ same condition
ROM1 p.Arg193Gly Uncertain significance ★★ ⚠ same condition
ROM1 p.Arg287Trp Uncertain significance ★★ ⚠ same condition
ROM1 p.Asp210Val Uncertain significance ★★ ⚠ same condition
ROM1 p.Asp317Gly 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/rom1-p-arg223 (accessed [today's date]).

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