Is EMC10 p.Ala41Val (c.122C>T) pathogenic?

EMC10 p.Ala41Val (c.122C>T) is classified Likely benign in EMC10 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-23). AlphaMissense: likely benign (0.0654); Ultra-rare (popmax 0.0167%, mid); Associated with Inborn genetic diseases.

What condition is associated with EMC10 p.Ala41Val (c.122C>T)?

EMC10 p.Ala41Val (c.122C>T) is associated with Inborn genetic diseases (ClinVar).

How common is EMC10 p.Ala41Val (c.122C>T) in the general population?

EMC10 p.Ala41Val (c.122C>T) is ultra-rare (popmax 0.0167%, mid) (gnomAD).

What do computational predictors say about EMC10 p.Ala41Val (c.122C>T)?

AlphaMissense predicts likely benign (score 0.0654) — an in-silico prediction, not a clinical call.

EMC10 p.Ala41Val

c.122C>T · VCV3844586

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0654 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0167%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0654	likely benign
REVEL	0.009	strongly benign-leaning
SaProt	LLR -8.11	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 -2.8
Regional constraint	o/e 1.12	unconstrained · MANE · 5,711 bp · p 0.019 · regional, not allelic
Overall
CADD	7.107	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 0.0167% Middle Eastern · 1/5,992 alleles

Filtering AF 0.0059% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00543%

Overall 0.00589% 94/1,597,128 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0167%	5,992
European (non-Finnish)	0.00715%	13,986
Remaining individualsnot grpmax-eligible	0.00486%	20,581
Finnishnot grpmax-eligible	0.00313%	31,911
African / African-American	0.00272%	36,746
Admixed American	0.00182%	55,070
South Asian	0.00113%	88,712

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: EMC10
Protein: p.Ala41Val
Coding: c.122C>T
MANE Select: NM_206538
Type: single nucleotide variant
Location: chr19:50477936 (GRCh38)
Gene constraint: LOEUF 1.606 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.60 · 10 PDB

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-ala41val (accessed [today's date]).

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