Is EFHC1 p.Phe308Ile (c.922T>A) pathogenic?

EFHC1 p.Phe308Ile (c.922T>A) is classified Uncertain significance in EFHC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2014-03-14). AlphaMissense: likely benign (0.3018); Absent from gnomAD v4.1.

How common is EFHC1 p.Phe308Ile (c.922T>A) in the general population?

EFHC1 p.Phe308Ile (c.922T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EFHC1 p.Phe308Ile (c.922T>A)?

AlphaMissense predicts likely benign (score 0.3018) — an in-silico prediction, not a clinical call.

EFHC1 p.Phe308Ile

c.922T>A · rs796052416 · VCV205399

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3018 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.3018	likely benign
REVEL	0.5	indeterminate
SaProt	LLR -3.26	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1.8, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 72 kb · p 0.035 · regional, not allelic
Overall
CADD	26.6	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: EFHC1
Protein: p.Phe308Ile
Coding: c.922T>A
MANE Select: NM_018100
dbSNP: rs796052416
Type: single nucleotide variant
Location: chr6:52464900 (GRCh38)
Gene constraint: LOEUF 0.906 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.31 · 2 PDB
Residue 308: the dm10 2 domain

Full EFHC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EFHC1 p.Ala445Thr Uncertain significance ★★ ⚠ same type
EFHC1 p.Ala529Glu Uncertain significance ★★ ⚠ same type
EFHC1 p.Ala590Pro Uncertain significance ★★ ⚠ same type
EFHC1 p.Ala83Val Uncertain significance ★★ ⚠ same type
EFHC1 p.Ala88Val Uncertain significance ★★ ⚠ same type
EFHC1 p.Arg118Cys Uncertain significance ★★ ⚠ same type
EFHC1 p.Arg151Leu Uncertain significance ★★ ⚠ same type
EFHC1 p.Arg159Gln 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/efhc1-p-phe308ile (accessed [today's date]).

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