Is RO60 p.Ala482Val (c.1445C>T) pathogenic?

RO60 p.Ala482Val (c.1445C>T) is classified Uncertain significance in RO60 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-24). AlphaMissense: likely benign (0.332); Absent from gnomAD v4.1.

How common is RO60 p.Ala482Val (c.1445C>T) in the general population?

RO60 p.Ala482Val (c.1445C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about RO60 p.Ala482Val (c.1445C>T)?

AlphaMissense predicts likely benign (score 0.332) — an in-silico prediction, not a clinical call.

RO60 p.Ala482Val

c.1445C>T · VCV4155972

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.332 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.332	likely benign
REVEL	0.313	indeterminate
SaProt	LLR -13.37	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 2.1, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 16 kb · p 0.00049 · regional, not allelic
Overall
CADD	26.4	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

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: RO60
Protein: p.Ala482Val
Coding: c.1445C>T
MANE Select: NM_001173524
Type: single nucleotide variant
Location: chr1:193082689 (GRCh38)
Gene constraint: LOEUF 0.519 · pLI 0.95 (gnomAD)
Structure: AlphaFold pLDDT 93.42 · 1 PDB
Residue 482: the 'vwfa-like domain' region

Full RO60 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

RO60 p.Lys270= Benign ★★ same type
RO60 p.Ala153Val Uncertain significance ★ ⚠ same type
RO60 p.Ala165Ser Uncertain significance ★ ⚠ same type
RO60 p.Ala317Asp Uncertain significance ★ same type
RO60 p.Ala461Thr Uncertain significance ★ ⚠ same type
RO60 p.Ala461Val Uncertain significance ★ ⚠ same type
RO60 p.Ala480Val Uncertain significance ★ ⚠ same type
RO60 p.Arg120His 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/ro60-p-ala482val (accessed [today's date]).

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