Is EMC1 p.Thr327Pro (c.979A>C) pathogenic?

EMC1 p.Thr327Pro (c.979A>C) is classified Uncertain significance in EMC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-01). AlphaMissense: likely benign (0.2834); Very rare (popmax 0.00223%, eas); Associated with inherited retinal dystrophy.

What condition is associated with EMC1 p.Thr327Pro (c.979A>C)?

EMC1 p.Thr327Pro (c.979A>C) is associated with inherited retinal dystrophy (ClinVar).

How common is EMC1 p.Thr327Pro (c.979A>C) in the general population?

EMC1 p.Thr327Pro (c.979A>C) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about EMC1 p.Thr327Pro (c.979A>C)?

AlphaMissense predicts likely benign (score 0.2834) — an in-silico prediction, not a clinical call.

EMC1 p.Thr327Pro

c.979A>C · rs2536775397 · VCV3028095

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2834 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

inherited retinal dystrophy

Computational evidence

Protein change
AlphaMissense	0.2834	likely benign
REVEL	0.338	indeterminate
SaProt	LLR -6.56	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.1	GERP 2, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 16 kb · p 0.24 · regional, not allelic
Overall
CADD	23.5	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

Grpmax group 0.00223% East Asian · 1/44,888 alleles

Overall 6.84e-05% 1/1,461,846 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.Thr327Pro
Coding: c.979A>C
MANE Select: NM_015047
dbSNP: rs2536775397
Type: single nucleotide variant
Location: chr1:19239278 (GRCh38)
Gene constraint: LOEUF 0.913 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.67 · 10 PDB
Residue 327: a β-strand

Full EMC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

inherited retinal dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

EMC1 p.Thr327Ser Uncertain significance ★★ ⚠ same residue
EMC1 p.Arg69Ter Pathogenic/Likely pathogenic ★★ same condition
EMC1 p.Ala21Thr Uncertain significance ★★ ⚠ same condition
EMC1 p.Arg275Gly Uncertain significance ★★ ⚠ same condition
EMC1 p.Arg275Trp Uncertain significance ★★ ⚠ same condition
EMC1 p.Arg288Trp Uncertain significance ★★ ⚠ same condition
EMC1 p.Arg384Trp Uncertain significance ★★ ⚠ same condition
EMC1 p.Arg802Cys 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-thr327pro (accessed [today's date]).

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