Is EMC1 p.Thr979Ile (c.2936C>T) pathogenic?

EMC1 p.Thr979Ile (c.2936C>T) is classified Uncertain significance in EMC1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-11-28). AlphaMissense: likely pathogenic (0.9631); Very rare (popmax 0.00167%, amr); Associated with Inborn genetic diseases.

What condition is associated with EMC1 p.Thr979Ile (c.2936C>T)?

EMC1 p.Thr979Ile (c.2936C>T) is associated with Inborn genetic diseases (ClinVar).

How common is EMC1 p.Thr979Ile (c.2936C>T) in the general population?

EMC1 p.Thr979Ile (c.2936C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about EMC1 p.Thr979Ile (c.2936C>T)?

AlphaMissense predicts likely pathogenic (score 0.9631) — an in-silico prediction, not a clinical call.

EMC1 p.Thr979Ile

c.2936C>T · rs770471010 · VCV1720876

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9631 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9631	likely pathogenic
REVEL	0.226	benign-leaning
SaProt	LLR -8.87	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.38 · evaluated, not missing
Constraint at this position
Conservation	phyloP 12	GERP 2.2, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 14 kb · p 4e-06 · regional, not allelic
Overall
CADD	27.5	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 0.00167% Admixed American · 1/60,008 alleles

Overall 6.84e-05% 1/1,461,886 alleles · very rare

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.Thr979Ile
Coding: c.2936C>T
MANE Select: NM_015047
dbSNP: rs770471010
Type: single nucleotide variant
Location: chr1:19219349 (GRCh38)
Gene constraint: LOEUF 0.913 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.67 · 10 PDB
Residue 979: an α-helix

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.Thr979Ser Uncertain significance ★ ⚠ same residue
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

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-thr979ile (accessed [today's date]).

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