Is EFHD1 p.Ser97Gly (c.289A>G) pathogenic?

EFHD1 p.Ser97Gly (c.289A>G) is classified Uncertain significance in EFHD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-03). AlphaMissense: likely benign (0.0592); Absent from gnomAD v4.1.

How common is EFHD1 p.Ser97Gly (c.289A>G) in the general population?

EFHD1 p.Ser97Gly (c.289A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EFHD1 p.Ser97Gly (c.289A>G)?

AlphaMissense predicts likely benign (score 0.0592) — an in-silico prediction, not a clinical call.

EFHD1 p.Ser97Gly

c.289A>G · VCV3507023

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0592 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0592	likely benign
REVEL	0.05	moderately benign-leaning
SaProt	LLR -5.24	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 0.4	GERP -3.1, phastCons 0.003
Regional constraint	o/e 0.95	unconstrained · MANE · 48 kb · p 0.33 · regional, not allelic
Overall
CADD	18.15	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: EFHD1
Protein: p.Ser97Gly
Coding: c.289A>G
MANE Select: NM_025202
Type: single nucleotide variant
Location: chr2:232633993 (GRCh38)
Gene constraint: LOEUF 1.121 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.10
Residue 97: the ef-hand 1 domain

Full EFHD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EFHD1 p.Ala124Thr Uncertain significance ★ ⚠ same type
EFHD1 p.Ala159Val Uncertain significance ★ ⚠ same type
EFHD1 p.Ala19Asp Uncertain significance ★ ⚠ same type
EFHD1 p.Ala49Pro Uncertain significance ★ ⚠ same type
EFHD1 p.Arg13Trp Uncertain significance ★ ⚠ same type
EFHD1 p.Arg149Gln Uncertain significance ★ ⚠ same type
EFHD1 p.Arg218Trp Uncertain significance ★ ⚠ same type
EFHD1 p.Arg224Gly 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/efhd1-p-ser97gly (accessed [today's date]).

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