Is MMUT p.Val487Phe (c.1459G>T) pathogenic?

MMUT p.Val487Phe (c.1459G>T) is classified Uncertain significance in MMUT (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-09). AlphaMissense: likely pathogenic (0.8901); Absent from gnomAD v4.1.

How common is MMUT p.Val487Phe (c.1459G>T) in the general population?

MMUT p.Val487Phe (c.1459G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MMUT p.Val487Phe (c.1459G>T)?

AlphaMissense predicts likely pathogenic (score 0.8901) — an in-silico prediction, not a clinical call.

MMUT p.Val487Phe

c.1459G>T · rs1767446389 · VCV1487103

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8901 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8901	likely pathogenic
REVEL	0.967	strongly pathogenic-leaning
SaProt	LLR -14.24	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 7.6	GERP 2.5, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 28 kb · p 0.059 · regional, not allelic
Overall
CADD	28.6	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: MMUT
Protein: p.Val487Phe
Coding: c.1459G>T
MANE Select: NM_000255
dbSNP: rs1767446389
Type: single nucleotide variant
Location: chr6:49447771 (GRCh38)
Gene constraint: LOEUF 1.18 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.72 · 6 PDB
Residue 487: a UniProt-annotated variant site (in mamm; mut-); a UniProt-annotated variant site (in mamm; mut0)

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

Similar variants

MMUT p.Val487Ala Uncertain significance ★ ⚠ same residue
MMUT c.1083+2T>A Pathogenic ★★ same type
MMUT c.1084-10A>G Pathogenic/Likely pathogenic ★★ same type
MMUT c.1084-2A>G Pathogenic/Likely pathogenic ★★ same type
MMUT c.1445-2A>G Pathogenic/Likely pathogenic ★★ same type
MMUT c.1560+1G>T Pathogenic ★★ same type
MMUT c.1677-1G>A Pathogenic ★★ same type
MMUT c.1677-1G>C Pathogenic/Likely pathogenic ★★ 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/mmut-p-val487phe (accessed [today's date]).

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