Is EMC7 p.Ala4Val (c.11C>T) pathogenic?

EMC7 p.Ala4Val (c.11C>T) is classified Uncertain significance in EMC7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-22). AlphaMissense: likely benign (0.1584); Ultra-rare (popmax 0.0386%, amr).

How common is EMC7 p.Ala4Val (c.11C>T) in the general population?

EMC7 p.Ala4Val (c.11C>T) is ultra-rare (popmax 0.0386%, amr) (gnomAD).

What do computational predictors say about EMC7 p.Ala4Val (c.11C>T)?

AlphaMissense predicts likely benign (score 0.1584) — an in-silico prediction, not a clinical call.

EMC7 p.Ala4Val

c.11C>T · VCV4664038

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1584 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0386%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1584	likely benign
REVEL	0.159	moderately benign-leaning
SaProt	LLR -7.02	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 5.5	GERP 1.8, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 11 kb · p 0.11 · regional, not allelic
Overall
CADD	18.37	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

Grpmax group 0.0386% Admixed American · 23/59,604 alleles

Filtering AF 0.0263% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0224%

Overall 0.00168% 27/1,604,610 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0386%	2,591
Middle Eastern	0.0333%	3,006
East Asian	0.00223%	44,822
European (non-Finnish)	8.49e-05%	1,177,876

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: EMC7
Protein: p.Ala4Val
Coding: c.11C>T
MANE Select: NM_020154
Type: single nucleotide variant
Location: chr15:34101829 (GRCh38)
Gene constraint: LOEUF 0.375 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 74.54 · 14 PDB

Full EMC7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EMC7 p.Gly38= Benign ★★ same type
EMC7 p.Ala238Pro Uncertain significance ★ ⚠ same type
EMC7 p.Ala30Val Uncertain significance ★ ⚠ same type
EMC7 p.Ala31Thr Uncertain significance ★ ⚠ same type
EMC7 p.Arg44His Uncertain significance ★ ⚠ same type
EMC7 p.Asp43Asn Uncertain significance ★ ⚠ same type
EMC7 p.Asp43His Uncertain significance ★ ⚠ same type
EMC7 p.Gly237Ala 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/emc7-p-ala4val (accessed [today's date]).

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