Is MECOM p.Phe172Val (c.514T>G) pathogenic?

MECOM p.Phe172Val (c.514T>G) is classified Uncertain significance in MECOM (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-23). AlphaMissense: likely pathogenic (0.5888); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with MECOM p.Phe172Val (c.514T>G)?

MECOM p.Phe172Val (c.514T>G) is associated with Inborn genetic diseases (ClinVar).

How common is MECOM p.Phe172Val (c.514T>G) in the general population?

MECOM p.Phe172Val (c.514T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MECOM p.Phe172Val (c.514T>G)?

AlphaMissense predicts likely pathogenic (score 0.5888) — an in-silico prediction, not a clinical call.

MECOM p.Phe172Val

c.514T>G · VCV3394283

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5888 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5888	likely pathogenic
REVEL	0.339	indeterminate
SaProt	LLR -9.75	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	Δ0.40	acceptor gain · deltas
Pangolin	Δ0.20	gain · loss 0.02 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 11	GERP 2.9, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 542 kb · p 0.0043 · regional, not allelic
Overall
CADD	32.0	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: MECOM
Protein: p.Phe172Val
Coding: c.514T>G
MANE Select: NM_004991
Type: single nucleotide variant
Location: chr3:169131528 (GRCh38)
Gene constraint: LOEUF 0.161 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 51.04 · 1 PDB
Residue 172: the set domain

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MECOM p.Phe172Leu Uncertain significance ★★ ⚠ same residue
MECOM p.Phe172Ser Uncertain significance ★ ⚠ same residue
MECOM p.Ala1022Gly Uncertain significance ★★ ⚠ same condition
MECOM p.Ala1228Val Uncertain significance ★★ ⚠ same condition
MECOM p.Ala222Val Uncertain significance ★★ ⚠ same condition
MECOM p.Ala434Val Uncertain significance ★★ ⚠ same condition
MECOM p.Ala477Gly Uncertain significance ★★ ⚠ same condition
MECOM p.Ala537Thr Uncertain significance ★★ ⚠ same condition

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/mecom-p-phe172val (accessed [today's date]).

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