Is ERI1 p.Cys139= (c.417T>C) pathogenic?

ERI1 p.Cys139= (c.417T>C) is classified Likely benign in ERI1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-03-20). Rare (popmax 0.762%, afr); Associated with ERI1-related disorder.

What condition is associated with ERI1 p.Cys139= (c.417T>C)?

ERI1 p.Cys139= (c.417T>C) is associated with ERI1-related disorder (ClinVar).

How common is ERI1 p.Cys139= (c.417T>C) in the general population?

ERI1 p.Cys139= (c.417T>C) is rare (popmax 0.762%, afr) (gnomAD).

ERI1 p.Cys139=

c.417T>C · rs143220656 · VCV3033956

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.762%, afr)

Conditions

ERI1-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP 2.1, phastCons 1
Overall
CADD	11.6	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.762% African / African-American · 572/75,052 alleles

Filtering AF 0.71% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.69%

Overall 0.0398% 642/1,613,744 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.762%	131
Middle Eastern	0.0825%	1,212
Remaining individualsnot grpmax-eligible	0.0544%	1,837
Admixed American	0.0317%	3,159
South Asian	0.00549%	18,212
European (non-Finnish)	0.000593%	168,533

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: ERI1
Protein: p.Cys139=
Coding: c.417T>C
MANE Select: NM_153332
dbSNP: rs143220656
Type: single nucleotide variant
Location: chr8:9011671 (GRCh38)
Gene constraint: LOEUF 1.526 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.04 · 5 PDB
Residue 139: a UniProt-annotated variant site (in semdgc; likely pathogenic); a UniProt-annotated variant site (in hxal; likely pathogenic); the exonuclease domain

Full ERI1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ERI1-related disorder

Similar variants

ERI1 p.Gln244Ter Likely pathogenic ★ same condition
ERI1 p.Lys237Asn Uncertain significance ★ ⚠ same condition
ERI1 c.582+10C>T Likely benign same condition
ERI1 c.583-9T>C Likely benign same condition
ERI1 p.Leu16Pro Benign same condition
ERI1 p.Pro24Arg Likely benign same condition
ERI1 p.Tyr109= Likely benign same condition
ERI1 c.109-11_109-6del Likely benign same condition

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/eri1-p-cys139 (accessed [today's date]).

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