Is ERICH6 p.Pro96Ser (c.286C>T) pathogenic?

ERICH6 p.Pro96Ser (c.286C>T) is classified Uncertain significance in ERICH6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-08). AlphaMissense: likely benign (0.1068); Ultra-rare (popmax 0.0133%, afr).

How common is ERICH6 p.Pro96Ser (c.286C>T) in the general population?

ERICH6 p.Pro96Ser (c.286C>T) is ultra-rare (popmax 0.0133%, afr) (gnomAD).

What do computational predictors say about ERICH6 p.Pro96Ser (c.286C>T)?

AlphaMissense predicts likely benign (score 0.1068) — an in-silico prediction, not a clinical call.

ERICH6 p.Pro96Ser

c.286C>T · VCV3846081

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1068 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0133%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1068	likely benign
REVEL	0.02	moderately benign-leaning
SaProt	LLR -5.15	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 2.1	GERP -1.7, phastCons 0.98
Regional constraint	o/e 1.03	unconstrained · MANE · 44 kb · p 0.37 · regional, not allelic
Overall
CADD	10.52	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 0.0133% African / African-American · 10/74,910 alleles

Filtering AF 0.00723% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0055%

Overall 0.000929% 15/1,613,930 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0133%	7,491
Remaining individualsnot grpmax-eligible	0.0048%	20,829
European (non-Finnish)	0.000169%	590,009

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: ERICH6
Protein: p.Pro96Ser
Coding: c.286C>T
MANE Select: NM_152394
Type: single nucleotide variant
Location: chr3:150703613 (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-pro96ser (accessed [today's date]).

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