Is ERICH6 p.Pro628Ser (c.1882C>T) pathogenic?

ERICH6 p.Pro628Ser (c.1882C>T) is classified Uncertain significance in ERICH6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-13). AlphaMissense: likely pathogenic (0.7744); Absent from gnomAD v4.1.

How common is ERICH6 p.Pro628Ser (c.1882C>T) in the general population?

ERICH6 p.Pro628Ser (c.1882C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ERICH6 p.Pro628Ser (c.1882C>T)?

AlphaMissense predicts likely pathogenic (score 0.7744) — an in-silico prediction, not a clinical call.

ERICH6 p.Pro628Ser

c.1882C>T · VCV4019549

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7744 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7744	likely pathogenic · top 9% in ERICH6
REVEL	0.358	indeterminate
SaProt	LLR -9.52	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.2, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 44 kb · p 0.37 · regional, not allelic
Overall
CADD	26.0	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

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.Pro628Ser
Coding: c.1882C>T
MANE Select: NM_152394
Type: single nucleotide variant
Location: chr3:150660002 (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-pro628ser (accessed [today's date]).

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