Is ERI2 p.Ser381Tyr (c.1142C>A) pathogenic?

ERI2 p.Ser381Tyr (c.1142C>A) is classified Uncertain significance in ERI2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-22). AlphaMissense: ambiguous (0.3583); Ultra-rare (popmax 0.0122%, eas).

How common is ERI2 p.Ser381Tyr (c.1142C>A) in the general population?

ERI2 p.Ser381Tyr (c.1142C>A) is ultra-rare (popmax 0.0122%, eas) (gnomAD).

What do computational predictors say about ERI2 p.Ser381Tyr (c.1142C>A)?

AlphaMissense predicts ambiguous (score 0.3583) — an in-silico prediction, not a clinical call.

ERI2 p.Ser381Tyr

c.1142C>A · VCV3276341

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3583 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0122%, eas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3583	ambiguous
REVEL	0.198	benign-leaning
SaProt	LLR -9.67	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.5	GERP 1.9, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 8,703 bp · p 0.00034 · regional, not allelic
Overall
CADD	23.6	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0122% East Asian · 5/40,928 alleles

Filtering AF 0.00479% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00308%

Overall 0.000322% 5/1,551,524 alleles · ultra-rare

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: ERI2
Protein: p.Ser381Tyr
Coding: c.1142C>A
MANE Select: NM_001142725
Type: single nucleotide variant
Location: chr16:20798658 (GRCh38)
Gene constraint: LOEUF 0.981 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 59.66 · 2 PDB

Full ERI2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ACSM3 p.Asn444His Uncertain significance ★ ⚠ same type
ACSM3 p.Gly260Ala Uncertain significance ★ ⚠ same type
ACSM3 p.Pro268Arg Uncertain significance ★ ⚠ same type
ACSM3 p.Trp273Arg Uncertain significance ★ ⚠ same type
ACSM3 p.Tyr457Cys Uncertain significance ★ ⚠ same type
ERI2 p.Ala102Ser Uncertain significance ★ ⚠ same type
ERI2 p.Ala19Val Uncertain significance ★ ⚠ same type
ERI2 p.Ala200Val 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/eri2-p-ser381tyr (accessed [today's date]).

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