Is ERMAP p.Val77Asp (c.230T>A) pathogenic?

ERMAP p.Val77Asp (c.230T>A) is classified Uncertain significance in ERMAP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-15). AlphaMissense: likely pathogenic (0.9774); Absent from gnomAD v4.1.

How common is ERMAP p.Val77Asp (c.230T>A) in the general population?

ERMAP p.Val77Asp (c.230T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ERMAP p.Val77Asp (c.230T>A)?

AlphaMissense predicts likely pathogenic (score 0.9774) — an in-silico prediction, not a clinical call.

ERMAP p.Val77Asp

c.230T>A · rs778168880 · VCV3090284

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9774 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.9774	likely pathogenic · top 2% in ERMAP
REVEL	0.557	indeterminate
SaProt	LLR -16.43	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 13 kb · p 0.085 · regional, not allelic
Overall
CADD	22.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ERMAP
Protein: p.Val77Asp
Coding: c.230T>A
MANE Select: NM_001017922
dbSNP: rs778168880
Type: single nucleotide variant
Location: chr1:42830912 (GRCh38)
Gene constraint: LOEUF 0.913 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.22
Residue 77: the ig-like v-type domain

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

Similar variants

ERMAP p.Ala4Val Benign ★★ same type
ERMAP p.Arg73= Benign ★★ same type
ERMAP p.Ala157Ser Uncertain significance ★ ⚠ same type
ERMAP p.Ala34Ser Uncertain significance ★ ⚠ same type
ERMAP p.Ala449Ser Uncertain significance ★ ⚠ same type
ERMAP p.Arg117His Uncertain significance ★ ⚠ same type
ERMAP p.Arg231Gly Uncertain significance ★ ⚠ same type
ERMAP p.Arg234Gln 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/ermap-p-val77asp (accessed [today's date]).

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