Is ERI1 p.Pro64Gln (c.191C>A) pathogenic?

ERI1 p.Pro64Gln (c.191C>A) is classified Uncertain significance in ERI1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-04). AlphaMissense: likely pathogenic (0.721); Very rare (popmax 0.000339%, nfe).

How common is ERI1 p.Pro64Gln (c.191C>A) in the general population?

ERI1 p.Pro64Gln (c.191C>A) is very rare (popmax 0.000339%, nfe) (gnomAD).

What do computational predictors say about ERI1 p.Pro64Gln (c.191C>A)?

AlphaMissense predicts likely pathogenic (score 0.721) — an in-silico prediction, not a clinical call.

ERI1 p.Pro64Gln

c.191C>A · rs750465484 · VCV2616306

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.721 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.721	likely pathogenic
REVEL	0.314	indeterminate
SaProt	LLR -10.92	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 7.6	GERP 1.6, phastCons 1
Regional constraint	o/e 1.39	unconstrained · MANE · 27 kb · p 9.3e-16 · regional, not allelic
Overall
CADD	25.7	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 0.000339% European (non-Finnish) · 4/1,178,290 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000249% 4/1,606,384 alleles · very rare exomes 4/1,460,534 · genomes 0/145,850 · joint denominator

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.Pro64Gln
Coding: c.191C>A
MANE Select: NM_153332
dbSNP: rs750465484
Type: single nucleotide variant
Location: chr8:9008052 (GRCh38)
Gene constraint: LOEUF 1.526 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.04 · 5 PDB
Residue 64: a UniProt-annotated variant site (in semdgc; likely pathogenic); an α-helix

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

Similar variants

ERI1 p.Pro64Leu Uncertain significance ★ ⚠ same residue
ERI1 p.Pro64Ser Uncertain significance ★ ⚠ same residue
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

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-pro64gln (accessed [today's date]).

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