Is EMP1 p.Cys142Ser (c.424T>A) pathogenic?

EMP1 p.Cys142Ser (c.424T>A) is classified Uncertain significance in EMP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-28). AlphaMissense: ambiguous (0.3719); Very rare (popmax 8.47e-05%, nfe).

How common is EMP1 p.Cys142Ser (c.424T>A) in the general population?

EMP1 p.Cys142Ser (c.424T>A) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about EMP1 p.Cys142Ser (c.424T>A)?

AlphaMissense predicts ambiguous (score 0.3719) — an in-silico prediction, not a clinical call.

EMP1 p.Cys142Ser

c.424T>A · VCV3844768

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3719 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Computational evidence

Protein change
AlphaMissense	0.3719	ambiguous
REVEL	0.617	indeterminate
SaProt	LLR -5.10	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP -0.26, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 3,177 bp · p 0.043 · regional, not allelic
Overall
CADD	21.8	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 8.47e-05% European (non-Finnish) · 1/1,179,992 alleles

Overall 6.84e-05% 1/1,461,874 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: EMP1
Protein: p.Cys142Ser
Coding: c.424T>A
MANE Select: NM_001423
Type: single nucleotide variant
Location: chr12:13214641 (GRCh38)
Gene constraint: LOEUF 0.629 · pLI 0.82 (gnomAD)
Structure: AlphaFold pLDDT 90.68

Full EMP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EMP1 p.Arg123Cys Uncertain significance ★ ⚠ same type
EMP1 p.Arg123Ser Uncertain significance ★ ⚠ same type
EMP1 p.Cys140Arg Uncertain significance ★ ⚠ same type
EMP1 p.Gln127His Uncertain significance ★ ⚠ same type
EMP1 p.Gly137Ser Uncertain significance ★ ⚠ same type
EMP1 p.Gly92Arg Uncertain significance ★ ⚠ same type
EMP1 p.Ile69Phe Uncertain significance ★ ⚠ same type
EMP1 p.Ile77Val 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/emp1-p-cys142ser (accessed [today's date]).

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