Is ERI3 p.Ser104Phe (c.311C>T) pathogenic?

ERI3 p.Ser104Phe (c.311C>T) is classified Uncertain significance in ERI3 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-26). AlphaMissense: likely benign (0.1482); Very rare (popmax 0.00167%, amr).

How common is ERI3 p.Ser104Phe (c.311C>T) in the general population?

ERI3 p.Ser104Phe (c.311C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about ERI3 p.Ser104Phe (c.311C>T)?

AlphaMissense predicts likely benign (score 0.1482) — an in-silico prediction, not a clinical call.

ERI3 p.Ser104Phe

c.311C>T · rs760666739 · VCV2218069

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1482 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1482	likely benign
REVEL	0.044	moderately benign-leaning
SaProt	LLR -7.51	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 10	GERP 2.8, phastCons 1
Regional constraint	o/e 0.55	unconstrained · MANE · 118 kb · p 1.7e-16 · regional, not allelic
Overall
CADD	25.9	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 0.00167% Admixed American · 1/59,990 alleles

Overall 6.84e-05% 1/1,461,856 alleles · very 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: ERI3
Protein: p.Ser104Phe
Coding: c.311C>T
MANE Select: NM_024066
dbSNP: rs760666739
Type: single nucleotide variant
Location: chr1:44339223 (GRCh38)
Gene constraint: LOEUF 0.651 · pLI 0.12 (gnomAD)
Structure: AlphaFold pLDDT 75.08 · 7 PDB

Full ERI3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ERI3 p.Ala229Val Uncertain significance ★ ⚠ same type
ERI3 p.Ala74Ser Uncertain significance ★ ⚠ same type
ERI3 p.Arg176Gln Uncertain significance ★ ⚠ same type
ERI3 p.Arg326Gln Uncertain significance ★ ⚠ same type
ERI3 p.Asp156Asn Uncertain significance ★ ⚠ same type
ERI3 p.Asp73Gly Uncertain significance ★ ⚠ same type
ERI3 p.Glu17Lys Uncertain significance ★ ⚠ same type
ERI3 p.Glu226Gly 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/eri3-p-ser104phe (accessed [today's date]).

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