Is ROM1 p.Arg97Ter (c.289C>T) pathogenic?

ROM1 p.Arg97Ter (c.289C>T) is classified Uncertain significance in ROM1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-04-08). Very rare (popmax 0.00801%, afr).

How common is ROM1 p.Arg97Ter (c.289C>T) in the general population?

ROM1 p.Arg97Ter (c.289C>T) is very rare (popmax 0.00801%, afr) (gnomAD).

ROM1 p.Arg97Ter

c.289C>T · rs201595136 · VCV840242

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00801%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 3
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.7	GERP -0.83
Overall
CADD	36.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00801% African / African-American · 6/74,910 alleles

Filtering AF 0.00519% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00474%

Overall 0.00527% 85/1,613,430 alleles · very rare exomes 77/1,461,256 · genomes 8/152,174 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00801%	12,485
European (non-Finnish)	0.00636%	15,730
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,584
Remaining individualsnot grpmax-eligible	0.0032%	31,218
South Asian	0.0011%	91,064

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.Arg97Ter
Coding: c.289C>T
MANE Select: NM_000327
dbSNP: rs201595136
Type: single nucleotide variant
Location: chr11:62613570 (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.Arg97Gln Uncertain significance ★★ ⚠ 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
ROM1 p.Ala71Thr 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-arg97ter (accessed [today's date]).

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