Is EFHC2 p.Pro393Ser (c.1177C>T) pathogenic?

EFHC2 p.Pro393Ser (c.1177C>T) is classified Uncertain significance in EFHC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-29). AlphaMissense: ambiguous (0.3423); No allele count reported in gnomAD v4.1 (AN 1,208,446).

How common is EFHC2 p.Pro393Ser (c.1177C>T) in the general population?

EFHC2 p.Pro393Ser (c.1177C>T) is no allele count reported in gnomAD v4.1 (AN 1,208,446) (gnomAD).

What do computational predictors say about EFHC2 p.Pro393Ser (c.1177C>T)?

AlphaMissense predicts ambiguous (score 0.3423) — an in-silico prediction, not a clinical call.

EFHC2 p.Pro393Ser

c.1177C>T · VCV4247091

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3423 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,208,446)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.3423	ambiguous
REVEL	0.719	pathogenic-leaning
SaProt	LLR -8.22	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 8.6	GERP 3.2, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 195 kb · p 0.037 · regional, not allelic
Overall
CADD	24.3	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

No allele count reported in gnomAD v4.1 (AN 1,208,446). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: EFHC2
Protein: p.Pro393Ser
Coding: c.1177C>T
MANE Select: NM_025184
Type: single nucleotide variant
Location: chrX:44242224 (GRCh38)
Structure: AlphaFold pLDDT 79.83 · 4 PDB

Full EFHC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EFHC2 p.Glu506Lys Likely benign ★★ same type
EFHC2 p.Glu507Gln Benign ★★ same type
EFHC2 p.Ala549Gly Uncertain significance ★ ⚠ same type
EFHC2 p.Ala697Ser Uncertain significance ★ ⚠ same type
EFHC2 p.Arg133His Uncertain significance ★ ⚠ same type
EFHC2 p.Arg135Gln Conflicting classifications of pathogenicity ★ ⚠ same type
EFHC2 p.Arg135Trp Uncertain significance ★ same type
EFHC2 p.Arg163Gln 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/efhc2-p-pro393ser (accessed [today's date]).

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