Is ERICH6 p.Val396Ala (c.1187T>C) pathogenic?

ERICH6 p.Val396Ala (c.1187T>C) is classified Uncertain significance in ERICH6 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-26). AlphaMissense: likely benign (0.0961); Absent from gnomAD v4.1.

How common is ERICH6 p.Val396Ala (c.1187T>C) in the general population?

ERICH6 p.Val396Ala (c.1187T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ERICH6 p.Val396Ala (c.1187T>C)?

AlphaMissense predicts likely benign (score 0.0961) — an in-silico prediction, not a clinical call.

ERICH6 p.Val396Ala

c.1187T>C · VCV3510157

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0961 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0961	likely benign
REVEL	0.051	moderately benign-leaning
SaProt	LLR -6.24	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>C here scores Δ0.24 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.12	GERP -2.4
Regional constraint	o/e 1.03	unconstrained · MANE · 44 kb · p 0.37 · regional, not allelic
Overall
CADD	0.527	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

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: ERICH6
Protein: p.Val396Ala
Coding: c.1187T>C
MANE Select: NM_152394
Type: single nucleotide variant
Location: chr3:150678479 (GRCh38)
Gene constraint: LOEUF 1.147 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.73

Full ERICH6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ERICH6 p.Ala320Gly Uncertain significance ★ ⚠ same type
ERICH6 p.Ala354Val Uncertain significance ★ ⚠ same type
ERICH6 p.Ala479Ser Uncertain significance ★ ⚠ same type
ERICH6 p.Ala562Ser Uncertain significance ★ ⚠ same type
ERICH6 p.Arg374Cys Uncertain significance ★ ⚠ same type
ERICH6 p.Arg414Pro Uncertain significance ★ ⚠ same type
ERICH6 p.Arg414Trp Uncertain significance ★ ⚠ same type
ERICH6 p.Arg458Gln 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/erich6-p-val396ala (accessed [today's date]).

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