Is ERICH3 p.Leu78Pro (c.233T>C) pathogenic?

ERICH3 p.Leu78Pro (c.233T>C) is classified Uncertain significance in ERICH3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-20). AlphaMissense: likely pathogenic (0.9928); Absent from gnomAD v4.1.

How common is ERICH3 p.Leu78Pro (c.233T>C) in the general population?

ERICH3 p.Leu78Pro (c.233T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ERICH3 p.Leu78Pro (c.233T>C)?

AlphaMissense predicts likely pathogenic (score 0.9928) — an in-silico prediction, not a clinical call.

ERICH3 p.Leu78Pro

c.233T>C · rs2523269718 · VCV2302740

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9928 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,372,012)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9928	likely pathogenic · top 1% in ERICH3
REVEL	0.564	indeterminate
SaProt	LLR -15.39	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 11	GERP 2.1, 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

No allele count reported in gnomAD v4.1 (AN 1,372,012). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ERICH3
Protein: p.Leu78Pro
Coding: c.233T>C
MANE Select: NM_001002912
dbSNP: rs2523269718
Type: single nucleotide variant
Location: chr1:74646677 (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.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
ERICH3 p.Ala1240Thr 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-leu78pro (accessed [today's date]).

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