Is EMC10 p.Val52Met (c.154G>A) pathogenic?

EMC10 p.Val52Met (c.154G>A) is classified Uncertain significance in EMC10 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-19). AlphaMissense: likely benign (0.1065); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with EMC10 p.Val52Met (c.154G>A)?

EMC10 p.Val52Met (c.154G>A) is associated with Inborn genetic diseases (ClinVar).

How common is EMC10 p.Val52Met (c.154G>A) in the general population?

EMC10 p.Val52Met (c.154G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EMC10 p.Val52Met (c.154G>A)?

AlphaMissense predicts likely benign (score 0.1065) — an in-silico prediction, not a clinical call.

EMC10 p.Val52Met

c.154G>A · VCV3844591

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1065 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1065	likely benign
REVEL	0.068	moderately benign-leaning
SaProt	LLR -8.37	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 1.6	GERP 0.18, phastCons 0.94
Regional constraint	o/e 1.12	unconstrained · MANE · 5,711 bp · p 0.019 · regional, not allelic
Overall
CADD	21.7	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

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: EMC10
Protein: p.Val52Met
Coding: c.154G>A
MANE Select: NM_206538
Type: single nucleotide variant
Location: chr19:50477968 (GRCh38)
Gene constraint: LOEUF 1.606 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.60 · 10 PDB
Residue 52: a β-strand

Full EMC10 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

EMC10 p.Arg97Ter Pathogenic ★★ same condition
EMC10 p.Ala134Val Uncertain significance ★★ ⚠ same condition
EMC10 p.Arg88Gln Uncertain significance ★★ ⚠ same condition
EMC10 p.Ser143Trp Uncertain significance ★★ ⚠ same condition
EMC10 p.Tyr127Cys Uncertain significance ★★ ⚠ same condition
EMC10 c.679-224C>T Uncertain significance ★ same condition
EMC10 p.Ala103Thr Uncertain significance ★ ⚠ same condition
EMC10 p.Ala224Thr 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/emc10-p-val52met (accessed [today's date]).

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