Is EMP1 p.Val83Met (c.247G>A) pathogenic?

EMP1 p.Val83Met (c.247G>A) is classified Uncertain significance in EMP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-25). AlphaMissense: likely benign (0.1528); Ultra-rare (popmax 0.0933%, sas).

How common is EMP1 p.Val83Met (c.247G>A) in the general population?

EMP1 p.Val83Met (c.247G>A) is ultra-rare (popmax 0.0933%, sas) (gnomAD).

What do computational predictors say about EMP1 p.Val83Met (c.247G>A)?

AlphaMissense predicts likely benign (score 0.1528) — an in-silico prediction, not a clinical call.

EMP1 p.Val83Met

c.247G>A · VCV4017900

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1528 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0933%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1528	likely benign
REVEL	0.25	benign-leaning
SaProt	LLR -8.40	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.26 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.73	GERP -3.5, phastCons 0.11
Regional constraint	o/e 0.85	unconstrained · MANE · 3,177 bp · p 0.043 · regional, not allelic
Overall
CADD	20.8	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 0.0933% South Asian · 85/91,066 alleles

Filtering AF 0.0773% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0713%

Overall 0.00774% 125/1,614,090 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0933%	1,071
Middle Eastern	0.0165%	6,062
African / African-American	0.00933%	10,715
Admixed American	0.00333%	30,008
Remaining individualsnot grpmax-eligible	0.0032%	31,254
European (non-Finnish)	0.00229%	43,705
East Asian	0.00223%	44,884

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.Val83Met
Coding: c.247G>A
MANE Select: NM_001423
Type: single nucleotide variant
Location: chr12:13213752 (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.Cys142Ser 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

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-val83met (accessed [today's date]).

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