Is EMC2 p.Thr201Ser (c.602C>G) pathogenic?

EMC2 p.Thr201Ser (c.602C>G) is classified Uncertain significance in EMC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-12). AlphaMissense: ambiguous (0.5636); Ultra-rare (popmax 0.0168%, mid).

How common is EMC2 p.Thr201Ser (c.602C>G) in the general population?

EMC2 p.Thr201Ser (c.602C>G) is ultra-rare (popmax 0.0168%, mid) (gnomAD).

What do computational predictors say about EMC2 p.Thr201Ser (c.602C>G)?

AlphaMissense predicts ambiguous (score 0.5636) — an in-silico prediction, not a clinical call.

EMC2 p.Thr201Ser

c.602C>G · rs762189951 · VCV2592752

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5636 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0168%, mid)

Computational evidence

Protein change
AlphaMissense	0.5636	ambiguous
REVEL	0.512	indeterminate
SaProt	LLR -9.71	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 43 kb · p 0.67 · regional, not allelic
Overall
CADD	24.9	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 0.0168% Middle Eastern · 1/5,962 alleles

Filtering AF 0.000642% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000494%

Overall 0.000898% 14/1,558,608 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0168%	5,962
European (non-Finnish)	0.00115%	86,970

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: EMC2
Protein: p.Thr201Ser
Coding: c.602C>G
MANE Select: NM_014673
dbSNP: rs762189951
Type: single nucleotide variant
Location: chr8:108476792 (GRCh38)
Gene constraint: LOEUF 1.84 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.40 · 11 PDB
Residue 201: an α-helix

Full EMC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EMC2 p.Ala271Thr Uncertain significance ★ ⚠ same type
EMC2 p.Arg273Gln Uncertain significance ★ ⚠ same type
EMC2 p.Asn167Ser Uncertain significance ★ ⚠ same type
EMC2 p.Asp111Gly Uncertain significance ★ ⚠ same type
EMC2 p.Asp287His Uncertain significance ★ ⚠ same type
EMC2 p.Gln134Glu Uncertain significance ★ ⚠ same type
EMC2 p.Gln293His Uncertain significance ★ ⚠ same type
EMC2 p.Glu286Lys 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/emc2-p-thr201ser (accessed [today's date]).

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