Is ROM1 p.Asp210Val (c.629A>T) pathogenic?

ROM1 p.Asp210Val (c.629A>T) is classified Uncertain significance in ROM1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-11-27). AlphaMissense: likely pathogenic (0.7614); Ultra-rare (popmax 0.0248%, nfe); Associated with inherited retinal dystrophy.

What condition is associated with ROM1 p.Asp210Val (c.629A>T)?

ROM1 p.Asp210Val (c.629A>T) is associated with inherited retinal dystrophy (ClinVar).

How common is ROM1 p.Asp210Val (c.629A>T) in the general population?

ROM1 p.Asp210Val (c.629A>T) is ultra-rare (popmax 0.0248%, nfe) (gnomAD).

What do computational predictors say about ROM1 p.Asp210Val (c.629A>T)?

AlphaMissense predicts likely pathogenic (score 0.7614) — an in-silico prediction, not a clinical call.

ROM1 p.Asp210Val

c.629A>T · rs200287184 · VCV636087

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely pathogenic

0.7614 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0248%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

inherited retinal dystrophy

Computational evidence

Protein change
AlphaMissense	0.7614	likely pathogenic · top 8% in ROM1
REVEL	0.817	moderately pathogenic-leaning
SaProt	LLR -16.03	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9	GERP 1.5, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 1,554 bp · p 0.86 · regional, not allelic
Overall
CADD	26.0	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

Grpmax group 0.0248% European (non-Finnish) · 293/1,180,002 alleles

Filtering AF 0.0225% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0216%

Overall 0.0193% 311/1,613,844 alleles · ultra-rare exomes 294/1,461,880 · genomes 17/151,964 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0248%	4,027
Remaining individualsnot grpmax-eligible	0.016%	6,248
Finnishnot grpmax-eligible	0.00625%	16,002
African / African-American	0.00535%	18,702

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.Asp210Val
Coding: c.629A>T
MANE Select: NM_000327
dbSNP: rs200287184
Type: single nucleotide variant
Location: chr11:62614296 (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

Similar variants

ROM1 p.Asp210Gly Uncertain significance ★ ⚠ same residue
ROM1 p.Arg287Trp Uncertain significance ★★ ⚠ same condition
ROM1 p.Gly111Trp Uncertain significance ★★ same condition
ROM1 p.Gly113Glu Uncertain significance ★★ ⚠ same condition
ROM1 p.Gly170Arg Uncertain significance ★★ ⚠ same condition
ROM1 p.Pro224Leu Uncertain significance ★★ ⚠ same condition
ROM1 p.Arg223= Benign ★★ same condition
ROM1 p.Arg229His Benign/Likely benign ★★ 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-asp210val (accessed [today's date]).

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