Is ERBIN p.Met396Val (c.1186A>G) pathogenic?

ERBIN p.Met396Val (c.1186A>G) is classified Uncertain significance in ERBIN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-08). AlphaMissense: ambiguous (0.3745); Ultra-rare (popmax 0.0246%, eas).

How common is ERBIN p.Met396Val (c.1186A>G) in the general population?

ERBIN p.Met396Val (c.1186A>G) is ultra-rare (popmax 0.0246%, eas) (gnomAD).

What do computational predictors say about ERBIN p.Met396Val (c.1186A>G)?

AlphaMissense predicts ambiguous (score 0.3745) — an in-silico prediction, not a clinical call.

ERBIN p.Met396Val

c.1186A>G · rs199814799 · VCV2171671

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3745 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0246%, eas)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3745	ambiguous
REVEL	0.248	benign-leaning
SaProt	LLR -10.12	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.1	GERP 4.1, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 56 kb · p 1.4e-05 · regional, not allelic
Overall
CADD	23.2	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 0.0246% East Asian · 11/44,744 alleles

Filtering AF 0.0137% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0106%

Overall 0.00112% 18/1,612,748 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0246%	4,068
Admixed American	0.00167%	59,948
African / African-American	0.00133%	75,020
South Asian	0.0011%	90,962
European (non-Finnish)	0.000339%	294,777

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: ERBIN
Protein: p.Met396Val
Coding: c.1186A>G
MANE Select: NM_001253697
dbSNP: rs199814799
Type: single nucleotide variant
Location: chr5:66028323 (GRCh38)
Gene constraint: LOEUF 0.526 · pLI 0.72 (gnomAD)
Structure: AlphaFold pLDDT 56.01 · 11 PDB

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

Similar variants

ERBIN p.Ala942Val Uncertain significance ★★ ⚠ same type
ERBIN p.Arg1096Gln Uncertain significance ★★ ⚠ same type
ERBIN p.Arg1166Gln Uncertain significance ★★ ⚠ same type
ERBIN p.Asn1035Ser Uncertain significance ★★ ⚠ same type
ERBIN p.Asn650Ser Uncertain significance ★★ ⚠ same type
ERBIN p.Asp530Tyr Uncertain significance ★★ ⚠ same type
ERBIN p.Cys658Ser Uncertain significance ★★ ⚠ same type
ERBIN p.His521Arg 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/erbin-p-met396val (accessed [today's date]).

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