Is ROM1 p.Ser84Arg (c.252C>G) pathogenic?

ROM1 p.Ser84Arg (c.252C>G) is classified Uncertain significance in ROM1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-11). AlphaMissense: likely pathogenic (0.8769); Absent from gnomAD v4.1.

How common is ROM1 p.Ser84Arg (c.252C>G) in the general population?

ROM1 p.Ser84Arg (c.252C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ROM1 p.Ser84Arg (c.252C>G)?

AlphaMissense predicts likely pathogenic (score 0.8769) — an in-silico prediction, not a clinical call.

ROM1 p.Ser84Arg

c.252C>G · rs2134421079 · VCV1349701

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8769 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.8769	likely pathogenic · top 5% in ROM1
REVEL	0.596	indeterminate
SaProt	LLR -11.36	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.56	GERP -0.78, phastCons 0.96
Regional constraint	o/e 0.99	unconstrained · MANE · 1,554 bp · p 0.86 · regional, not allelic
Overall
CADD	21.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ROM1
Protein: p.Ser84Arg
Coding: c.252C>G
MANE Select: NM_000327
dbSNP: rs2134421079
Type: single nucleotide variant
Location: chr11:62613533 (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.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
ROM1 p.Ala71Thr Uncertain significance ★★ ⚠ same type
ROM1 p.Ala71Val 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-ser84arg (accessed [today's date]).

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