Is EMC2 p.Tyr44His (c.130T>C) pathogenic?

EMC2 p.Tyr44His (c.130T>C) is classified Uncertain significance in EMC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-02). AlphaMissense: likely benign (0.1293); Absent from gnomAD v4.1.

How common is EMC2 p.Tyr44His (c.130T>C) in the general population?

EMC2 p.Tyr44His (c.130T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EMC2 p.Tyr44His (c.130T>C)?

AlphaMissense predicts likely benign (score 0.1293) — an in-silico prediction, not a clinical call.

EMC2 p.Tyr44His

c.130T>C · VCV3508151

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1293 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,568,502)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1293	likely benign
REVEL	0.061	moderately benign-leaning
SaProt	LLR -6.87	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 6.2	GERP 2, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 43 kb · p 0.67 · regional, not allelic
Overall
CADD	18.23	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

No allele count reported in gnomAD v4.1 (AN 1,568,502). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: EMC2
Protein: p.Tyr44His
Coding: c.130T>C
MANE Select: NM_014673
Type: single nucleotide variant
Location: chr8:108449912 (GRCh38)
Gene constraint: LOEUF 1.84 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.40 · 11 PDB

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-tyr44his (accessed [today's date]).

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