Is ROM1 p.Arg198Pro (c.593G>C) pathogenic?

ROM1 p.Arg198Pro (c.593G>C) is classified Uncertain significance in ROM1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-08). AlphaMissense: likely pathogenic (0.8675); Very rare (popmax 0.00167%, amr).

How common is ROM1 p.Arg198Pro (c.593G>C) in the general population?

ROM1 p.Arg198Pro (c.593G>C) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about ROM1 p.Arg198Pro (c.593G>C)?

AlphaMissense predicts likely pathogenic (score 0.8675) — an in-silico prediction, not a clinical call.

ROM1 p.Arg198Pro

c.593G>C · VCV3730832

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8675 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8675	likely pathogenic · top 5% in ROM1
REVEL	0.23	benign-leaning
SaProt	LLR -11.97	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>A here scores Δ0.31 · evaluated, not missing
Constraint at this position
Conservation	phyloP 3.3	GERP 1.5, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 1,554 bp · p 0.86 · regional, not allelic
Overall
CADD	25.5	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 0.00167% Admixed American · 1/60,000 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000186% 3/1,613,958 alleles · very rare exomes 3/1,461,858 · genomes 0/152,100 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,000
European (non-Finnish)	0.000169%	589,988

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.Arg198Pro
Coding: c.593G>C
MANE Select: NM_000327
Type: single nucleotide variant
Location: chr11:62614260 (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

Similar variants

ROM1 p.Arg198Trp Uncertain significance ★★ ⚠ same residue
ROM1 p.Arg198Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
ROM1 p.Ala132Val Uncertain significance ★★ ⚠ same type
ROM1 p.Ala140Thr Uncertain significance ★★ ⚠ same type
ROM1 p.Ala265Thr Uncertain significance ★★ ⚠ same type
ROM1 p.Ala329Val Uncertain significance ★★ ⚠ same type
ROM1 p.Ala54Thr Uncertain significance ★★ ⚠ same type
ROM1 p.Ala69Gly 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/rom1-p-arg198pro (accessed [today's date]).

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