Is EMC1 p.Ser917Thr (c.2749T>A) pathogenic?

EMC1 p.Ser917Thr (c.2749T>A) is classified Uncertain significance in EMC1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-17). AlphaMissense: likely benign (0.1014); Ultra-rare (popmax 0.0401%, afr); Associated with Inborn genetic diseases.

What condition is associated with EMC1 p.Ser917Thr (c.2749T>A)?

EMC1 p.Ser917Thr (c.2749T>A) is associated with Inborn genetic diseases (ClinVar).

How common is EMC1 p.Ser917Thr (c.2749T>A) in the general population?

EMC1 p.Ser917Thr (c.2749T>A) is ultra-rare (popmax 0.0401%, afr) (gnomAD).

What do computational predictors say about EMC1 p.Ser917Thr (c.2749T>A)?

AlphaMissense predicts likely benign (score 0.1014) — an in-silico prediction, not a clinical call.

EMC1 p.Ser917Thr

c.2749T>A · rs529971469 · VCV1024226

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1014 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0401%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1014	likely benign
REVEL	0.104	moderately benign-leaning
SaProt	LLR -7.24	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 6.9	GERP 1.1, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 14 kb · p 4e-06 · regional, not allelic
Overall
CADD	20.2	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 0.0401% African / African-American · 30/74,724 alleles

Filtering AF 0.0289% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.025%

Overall 0.00211% 34/1,613,276 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0401%	2,491
Admixed American	0.00501%	19,979
European (non-Finnish)	8.48e-05%	1,179,736

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.Ser917Thr
Coding: c.2749T>A
MANE Select: NM_015047
dbSNP: rs529971469
Type: single nucleotide variant
Location: chr1:19219622 (GRCh38)
Gene constraint: LOEUF 0.913 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.67 · 10 PDB
Residue 917: a β-strand

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.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
EMC1 p.Ala637Thr 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-ser917thr (accessed [today's date]).

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