Is ERICH3 p.Gln337Pro (c.1010A>C) pathogenic?

ERICH3 p.Gln337Pro (c.1010A>C) is classified Uncertain significance in ERICH3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-05). AlphaMissense: likely pathogenic (0.9618); Very rare (popmax 0.00313%, nfe).

How common is ERICH3 p.Gln337Pro (c.1010A>C) in the general population?

ERICH3 p.Gln337Pro (c.1010A>C) is very rare (popmax 0.00313%, nfe) (gnomAD).

What do computational predictors say about ERICH3 p.Gln337Pro (c.1010A>C)?

AlphaMissense predicts likely pathogenic (score 0.9618) — an in-silico prediction, not a clinical call.

ERICH3 p.Gln337Pro

c.1010A>C · VCV4019502

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9618 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00313%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9618	likely pathogenic · top 3% in ERICH3
REVEL	0.372	indeterminate
SaProt	LLR -13.59	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 2.3, phastCons 1
Regional constraint	o/e 1.13	unconstrained · MANE · 102 kb · p 1.9e-08 · regional, not allelic
Overall
CADD	26.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00313% European (non-Finnish) · 36/1,151,668 alleles

Filtering AF 0.00229% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00203%

Overall 0.00235% 37/1,576,140 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00313%	31,991
African / African-American	0.00134%	74,370

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: ERICH3
Protein: p.Gln337Pro
Coding: c.1010A>C
MANE Select: NM_001002912
Type: single nucleotide variant
Location: chr1:74612800 (GRCh38)
Gene constraint: LOEUF 1.119 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 44.25

Full ERICH3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ERICH3 p.Gln337Arg Uncertain significance ★ ⚠ same residue
ERICH3 p.Ala1022Gly Uncertain significance ★ ⚠ same type
ERICH3 p.Ala1083Glu Uncertain significance ★ ⚠ same type
ERICH3 p.Ala1100Val Uncertain significance ★ ⚠ same type
ERICH3 p.Ala1117Ser Uncertain significance ★ ⚠ same type
ERICH3 p.Ala1185Val Uncertain significance ★ ⚠ same type
ERICH3 p.Ala1215Ser Uncertain significance ★ ⚠ same type
ERICH3 p.Ala1218Thr 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/erich3-p-gln337pro (accessed [today's date]).

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