Is MME p.Ser142Phe (c.425C>T) pathogenic?

MME p.Ser142Phe (c.425C>T) is classified Uncertain significance in MME (ClinVar, Single submitter, 1 submitter; last evaluated 2026-03-11). AlphaMissense: likely pathogenic (0.9831); Absent from gnomAD v4.1.

How common is MME p.Ser142Phe (c.425C>T) in the general population?

MME p.Ser142Phe (c.425C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MME p.Ser142Phe (c.425C>T)?

AlphaMissense predicts likely pathogenic (score 0.9831) — an in-silico prediction, not a clinical call.

MME p.Ser142Phe

c.425C>T · VCV4891460

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9831 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.9831	likely pathogenic · top 8% in MME
REVEL	0.63	indeterminate
SaProt	LLR -14.87	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.86 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.7	GERP 2.4, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 96 kb · p 0.045 · regional, not allelic
Overall
CADD	28.2	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: MME
Protein: p.Ser142Phe
Coding: c.425C>T
MANE Select: NM_007289
Type: single nucleotide variant
Location: chr3:155116545 (GRCh38)
Gene constraint: LOEUF 0.931 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.25 · 16 PDB
Residue 142: an α-helix; the peptidase m13 domain

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

Similar variants

MME c.1497+1G>A Likely pathogenic ★★ same type
MME c.1497+1G>C Likely pathogenic ★★ same type
MME c.160+2T>C Likely pathogenic ★★ same type
MME c.1601+2T>C Likely pathogenic ★★ same type
MME c.1781-2A>G Pathogenic/Likely pathogenic ★★ same type
MME c.439+1G>A Likely pathogenic ★★ same type
MME c.440-2A>C Pathogenic/Likely pathogenic ★★ same type
MME c.536-1G>A 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/mme-p-ser142phe (accessed [today's date]).

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