Is EMC1 p.Ala2Val (c.5C>T) pathogenic?

EMC1 p.Ala2Val (c.5C>T) is classified Uncertain significance in EMC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-19). AlphaMissense: likely benign (0.2676); Ultra-rare (popmax 0.0757%, eas).

How common is EMC1 p.Ala2Val (c.5C>T) in the general population?

EMC1 p.Ala2Val (c.5C>T) is ultra-rare (popmax 0.0757%, eas) (gnomAD).

What do computational predictors say about EMC1 p.Ala2Val (c.5C>T)?

AlphaMissense predicts likely benign (score 0.2676) — an in-silico prediction, not a clinical call.

EMC1 p.Ala2Val

c.5C>T · rs749957590 · VCV963796

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2676 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0757%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2676	likely benign
REVEL	0.168	moderately benign-leaning
SaProt	LLR -7.87	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 2.4	GERP 0.62, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 16 kb · p 0.24 · regional, not allelic
Overall
CADD	22.2	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 0.0757% East Asian · 34/44,900 alleles

Filtering AF 0.0557% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0488%

Overall 0.00229% 37/1,613,982 alleles · ultra-rare exomes 31/1,461,734 · genomes 6/152,248 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0757%	1,321
Remaining individualsnot grpmax-eligible	0.0048%	20,829

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: EMC1
Protein: p.Ala2Val
Coding: c.5C>T
MANE Select: NM_015047
dbSNP: rs749957590
Type: single nucleotide variant
Location: chr1:19251505 (GRCh38)
Gene constraint: LOEUF 0.913 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.67 · 10 PDB

Full EMC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EMC1 p.Ala2Gly Uncertain significance ★ ⚠ same residue
EMC1 p.Ala2= Likely benign ★ same residue
EMC1 c.287-1G>A Likely pathogenic ★★ same type
EMC1 c.787-1G>A Likely pathogenic ★★ same type
EMC1 p.Arg105Ter Pathogenic/Likely pathogenic ★★ same type
EMC1 p.Arg660Ter Pathogenic/Likely pathogenic ★★ same type
EMC1 p.Arg687Ter Pathogenic/Likely pathogenic ★★ same type
EMC1 p.Arg69Ter 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/emc1-p-ala2val (accessed [today's date]).

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