Is ERICH1 p.Pro20Ser (c.58C>T) pathogenic?

ERICH1 p.Pro20Ser (c.58C>T) is classified Uncertain significance in ERICH1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-26). AlphaMissense: likely benign (0.0939); Very rare (popmax 0.0077%, sas).

How common is ERICH1 p.Pro20Ser (c.58C>T) in the general population?

ERICH1 p.Pro20Ser (c.58C>T) is very rare (popmax 0.0077%, sas) (gnomAD).

What do computational predictors say about ERICH1 p.Pro20Ser (c.58C>T)?

AlphaMissense predicts likely benign (score 0.0939) — an in-silico prediction, not a clinical call.

ERICH1 p.Pro20Ser

c.58C>T · rs565378212 · VCV2541203

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0939 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0077%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0939	likely benign
REVEL	0.014	strongly benign-leaning
SaProt	LLR -1.82	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 -0.59	GERP -2.8
Regional constraint	o/e 1.44	unconstrained · MANE · 67 kb · p 1.5e-25 · regional, not allelic
Overall
CADD	0.022	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 0.0077% South Asian · 7/90,922 alleles

Filtering AF 0.00359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00255%

Overall 0.00118% 19/1,613,228 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0077%	12,989
European (non-Finnish)	0.00102%	98,312

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: ERICH1
Protein: p.Pro20Ser
Coding: c.58C>T
MANE Select: NM_207332
dbSNP: rs565378212
Type: single nucleotide variant
Location: chr8:715972 (GRCh38)
Gene constraint: LOEUF 1.79 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.82
Residue 20: the 'disordered' region

Full ERICH1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ERICH1 p.Ala176Glu Uncertain significance ★ ⚠ same type
ERICH1 p.Ala221Thr Uncertain significance ★ ⚠ same type
ERICH1 p.Ala235Val Uncertain significance ★ ⚠ same type
ERICH1 p.Ala269Pro Uncertain significance ★ ⚠ same type
ERICH1 p.Ala299Val Uncertain significance ★ ⚠ same type
ERICH1 p.Ala360Pro Uncertain significance ★ ⚠ same type
ERICH1 p.Ala364Asp Uncertain significance ★ ⚠ same type
ERICH1 p.Ala366Ser 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/erich1-p-pro20ser (accessed [today's date]).

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