Is EMC1 p.Ile143Phe (c.427A>T) pathogenic?

EMC1 p.Ile143Phe (c.427A>T) is classified Uncertain significance in EMC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-27). AlphaMissense: likely benign (0.2257); Very rare (popmax 0.00267%, afr).

How common is EMC1 p.Ile143Phe (c.427A>T) in the general population?

EMC1 p.Ile143Phe (c.427A>T) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about EMC1 p.Ile143Phe (c.427A>T)?

AlphaMissense predicts likely benign (score 0.2257) — an in-silico prediction, not a clinical call.

EMC1 p.Ile143Phe

c.427A>T · rs536488842 · VCV1015023

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2257 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2257	likely benign
REVEL	0.055	moderately benign-leaning
SaProt	LLR -10.78	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -4.1	GERP -4.2
Regional constraint	o/e 0.95	unconstrained · MANE · 16 kb · p 0.24 · regional, not allelic
Overall
CADD	0.25	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 0.00267% African / African-American · 2/74,916 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.00131% 2/152,182 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.Ile143Phe
Coding: c.427A>T
MANE Select: NM_015047
dbSNP: rs536488842
Type: single nucleotide variant
Location: chr1:19242427 (GRCh38)
Gene constraint: LOEUF 0.913 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.67 · 10 PDB
Residue 143: a β-strand

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

Similar variants

EMC1 p.Ile143= Likely benign ★★ same residue
EMC1 c.287-1G>A Likely pathogenic ★★ same type
EMC1 c.787-1G>A Likely pathogenic ★★ same type
EMC1 p.Arg105Ter Pathogenic/Likely pathogenic ★★ same type
EMC1 p.Arg660Ter Pathogenic/Likely pathogenic ★★ same type
EMC1 p.Arg687Ter Pathogenic/Likely pathogenic ★★ same type
EMC1 p.Arg69Ter Pathogenic/Likely pathogenic ★★ same type
EMC1 p.Arg908Ter Pathogenic ★★ 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/emc1-p-ile143phe (accessed [today's date]).

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