Is EMC1 p.Ala3Val (c.8C>T) pathogenic?

EMC1 p.Ala3Val (c.8C>T) is classified Conflicting classifications of pathogenicity in EMC1 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-12-10). AlphaMissense: likely benign (0.1985); Ultra-rare (popmax 0.0735%, eas); Associated with Inborn genetic diseases.

What condition is associated with EMC1 p.Ala3Val (c.8C>T)?

EMC1 p.Ala3Val (c.8C>T) is associated with Inborn genetic diseases (ClinVar).

How common is EMC1 p.Ala3Val (c.8C>T) in the general population?

EMC1 p.Ala3Val (c.8C>T) is ultra-rare (popmax 0.0735%, eas) (gnomAD).

What do computational predictors say about EMC1 p.Ala3Val (c.8C>T)?

AlphaMissense predicts likely benign (score 0.1985) — an in-silico prediction, not a clinical call.

EMC1 p.Ala3Val

c.8C>T · rs552276163 · VCV837771

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1985 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0735%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1985	likely benign
REVEL	0.047	moderately benign-leaning
SaProt	LLR -6.92	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.67 · evaluated, not missing
Constraint at this position
Conservation	phyloP 3.7	GERP 1.7, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 16 kb · p 0.24 · regional, not allelic
Overall
CADD	20.3	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

Grpmax group 0.0735% East Asian · 33/44,886 alleles

Filtering AF 0.0538% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.047%

Overall 0.00217% 35/1,614,106 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0735%	1,360
European (non-Finnish)	0.000169%	590,012

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.Ala3Val
Coding: c.8C>T
MANE Select: NM_015047
dbSNP: rs552276163
Type: single nucleotide variant
Location: chr1:19251502 (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

Disease context

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

Similar variants

EMC1 p.Thr82Met Pathogenic/Likely pathogenic ★★ ⚠ same condition
EMC1 c.1782+3G>A Uncertain significance ★★ same condition
EMC1 c.509+6G>A Uncertain significance ★★ same condition
EMC1 p.Ala152Val Uncertain significance ★★ ⚠ same condition
EMC1 p.Ala21Thr Uncertain significance ★★ ⚠ same condition
EMC1 p.Ala43Val Uncertain significance ★★ ⚠ same condition
EMC1 p.Ala509Val Uncertain significance ★★ ⚠ same condition
EMC1 p.Ala637Thr 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/emc1-p-ala3val (accessed [today's date]).

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