Is ROM1 p.Pro6Ser (c.16C>T) pathogenic?

ROM1 p.Pro6Ser (c.16C>T) is classified Uncertain significance in ROM1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-01). AlphaMissense: likely benign (0.14); No allele count reported in gnomAD v4.1 (AN 1,607,486).

How common is ROM1 p.Pro6Ser (c.16C>T) in the general population?

ROM1 p.Pro6Ser (c.16C>T) is no allele count reported in gnomAD v4.1 (AN 1,607,486) (gnomAD).

What do computational predictors say about ROM1 p.Pro6Ser (c.16C>T)?

AlphaMissense predicts likely benign (score 0.14) — an in-silico prediction, not a clinical call.

ROM1 p.Pro6Ser

c.16C>T · rs2496219478 · VCV1711318

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.14 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,607,486)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.14	likely benign
REVEL	0.042	moderately benign-leaning
SaProt	LLR -9.16	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.8	GERP 0.18, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 1,554 bp · p 0.86 · regional, not allelic
Overall
CADD	20.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

No allele count reported in gnomAD v4.1 (AN 1,607,486). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ROM1
Protein: p.Pro6Ser
Coding: c.16C>T
MANE Select: NM_000327
dbSNP: rs2496219478
Type: single nucleotide variant
Location: chr11:62613297 (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-pro6ser (accessed [today's date]).

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