Is EMC3 p.Asn175Ser (c.524A>G) pathogenic?

EMC3 p.Asn175Ser (c.524A>G) is classified Uncertain significance in EMC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-01). AlphaMissense: ambiguous (0.4674); Very rare (popmax 8.47e-05%, nfe).

How common is EMC3 p.Asn175Ser (c.524A>G) in the general population?

EMC3 p.Asn175Ser (c.524A>G) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about EMC3 p.Asn175Ser (c.524A>G)?

AlphaMissense predicts ambiguous (score 0.4674) — an in-silico prediction, not a clinical call.

EMC3 p.Asn175Ser

c.524A>G · VCV3275266

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4674 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Computational evidence

Protein change
AlphaMissense	0.4674	ambiguous
REVEL	0.401	indeterminate
SaProt	LLR -10.41	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.48	unconstrained · MANE · 9,545 bp · p 1.7e-08 · regional, not allelic
Overall
CADD	27.4	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 8.47e-05% European (non-Finnish) · 1/1,180,024 alleles

Overall 6.2e-05% 1/1,613,968 alleles · very rare exomes 0/1,461,876 · genomes 1/152,092 · joint denominator

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: EMC3
Protein: p.Asn175Ser
Coding: c.524A>G
MANE Select: NM_001394674
Type: single nucleotide variant
Location: chr3:9970632 (GRCh38)
Gene constraint: LOEUF 0.548 · pLI 0.92 (gnomAD)
Structure: AlphaFold pLDDT 78.38 · 10 PDB
Residue 175: an α-helix

Full EMC3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EMC3 c.-242+3401G>A Uncertain significance ★ same type
EMC3 c.-242+3659C>G Uncertain significance ★ same type
EMC3 p.Ala212Thr Uncertain significance ★ ⚠ same type
EMC3 p.Arg180Trp Uncertain significance ★ ⚠ same type
EMC3 p.Arg57Gln Uncertain significance ★ ⚠ same type
EMC3 p.Arg93Trp Uncertain significance ★ ⚠ same type
EMC3 p.Asp41Asn Uncertain significance ★ ⚠ same type
EMC3 p.Asp41His 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/emc3-p-asn175ser (accessed [today's date]).

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