Is ERI1 p.Gln40Pro (c.119A>C) pathogenic?

ERI1 p.Gln40Pro (c.119A>C) is classified Uncertain significance in ERI1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-02). AlphaMissense: likely benign (0.0616); Ultra-rare (popmax 0.0149%, nfe).

How common is ERI1 p.Gln40Pro (c.119A>C) in the general population?

ERI1 p.Gln40Pro (c.119A>C) is ultra-rare (popmax 0.0149%, nfe) (gnomAD).

What do computational predictors say about ERI1 p.Gln40Pro (c.119A>C)?

AlphaMissense predicts likely benign (score 0.0616) — an in-silico prediction, not a clinical call.

ERI1 p.Gln40Pro

c.119A>C · rs374437030 · VCV2368302

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0616 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0149%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0616	likely benign
REVEL	0.032	moderately benign-leaning
SaProt	LLR -4.82	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 0.43	GERP -2.8, phastCons 0.001
Regional constraint	o/e 1.39	unconstrained · MANE · 27 kb · p 9.3e-16 · regional, not allelic
Overall
CADD	4.102	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 0.0149% European (non-Finnish) · 124/832,188 alleles

Filtering AF 0.0128% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.012%

Overall 0.0115% 132/1,152,380 alleles · ultra-rare exomes 128/1,036,944 · genomes 4/115,436 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0149%	6,711
Remaining individualsnot grpmax-eligible	0.0114%	8,793
African / African-American	0.00357%	28,048
Admixed American	0.00255%	39,158

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.Gln40Pro
Coding: c.119A>C
MANE Select: NM_153332
dbSNP: rs374437030
Type: single nucleotide variant
Location: chr8:9007980 (GRCh38)
Gene constraint: LOEUF 1.526 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.04 · 5 PDB
Residue 40: a UniProt-annotated variant site (in semdgc; likely pathogenic); the 'disordered' region

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

Similar variants

ERI1 p.Ser333Tyr Uncertain significance ★★ ⚠ same type
ERI1 p.Thr221Ala Uncertain significance ★★ ⚠ same type
ERI1 p.Arg291= Benign ★★ same type
ERI1 p.Arg304Ter Likely pathogenic ★ same type
ERI1 p.Asp134Gly Likely pathogenic ★ same type
ERI1 p.Asp298Gly Likely pathogenic ★ same type
ERI1 p.Gln244Ter Likely pathogenic ★ same type
ERI1 p.Glu150Asp Likely pathogenic ★ 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/eri1-p-gln40pro (accessed [today's date]).

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