Is ERMN p.Asp169Val (c.506A>T) pathogenic?

ERMN p.Asp169Val (c.506A>T) is classified Uncertain significance in ERMN (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-02). AlphaMissense: likely benign (0.1272); Very rare (popmax 0.00542%, nfe).

How common is ERMN p.Asp169Val (c.506A>T) in the general population?

ERMN p.Asp169Val (c.506A>T) is very rare (popmax 0.00542%, nfe) (gnomAD).

What do computational predictors say about ERMN p.Asp169Val (c.506A>T)?

AlphaMissense predicts likely benign (score 0.1272) — an in-silico prediction, not a clinical call.

ERMN p.Asp169Val

c.506A>T · rs776307442 · VCV2507869

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1272 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00542%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1272	likely benign
REVEL	0.038	moderately benign-leaning
SaProt	LLR -6.69	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 0.96	GERP -1.2, phastCons 0.001
Regional constraint	o/e 1.05	unconstrained · MANE · 4,368 bp · p 0.37 · regional, not allelic
Overall
CADD	13.19	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 0.00542% European (non-Finnish) · 64/1,180,008 alleles

Filtering AF 0.00435% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00396%

Overall 0.00415% 67/1,614,032 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00542%	18,438
Remaining individualsnot grpmax-eligible	0.0048%	20,829

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: ERMN
Protein: p.Asp169Val
Coding: c.506A>T
MANE Select: NM_020711
dbSNP: rs776307442
Type: single nucleotide variant
Location: chr2:157321620 (GRCh38)
Gene constraint: LOEUF 0.963 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 57.95
Residue 169: the 'disordered' region

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

Similar variants

ERMN p.Ala52Thr Benign ★★ same type
ERMN c.-27T>G Uncertain significance ★ same type
ERMN p.Ala11Asp Uncertain significance ★ ⚠ same type
ERMN p.Ala93Pro Uncertain significance ★ ⚠ same type
ERMN p.Arg110Gly Uncertain significance ★ ⚠ same type
ERMN p.Arg128Gly Uncertain significance ★ ⚠ same type
ERMN p.Arg147Gly Uncertain significance ★ ⚠ same type
ERMN p.Arg163Leu 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/ermn-p-asp169val (accessed [today's date]).

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