Is EFHC1 p.Pro13Ser (c.37C>T) pathogenic?

EFHC1 p.Pro13Ser (c.37C>T) is classified Uncertain significance in EFHC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-20). AlphaMissense: ambiguous (0.5351); Ultra-rare (popmax 0.0164%, mid).

How common is EFHC1 p.Pro13Ser (c.37C>T) in the general population?

EFHC1 p.Pro13Ser (c.37C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about EFHC1 p.Pro13Ser (c.37C>T)?

AlphaMissense predicts ambiguous (score 0.5351) — an in-silico prediction, not a clinical call.

EFHC1 p.Pro13Ser

c.37C>T · rs754282571 · VCV3087544

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5351 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5351	ambiguous
REVEL	0.83	moderately pathogenic-leaning
SaProt	LLR -9.06	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP 1.4, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 72 kb · p 0.035 · regional, not allelic
Overall
CADD	26.2	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 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.00347% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00228%

Overall 0.000434% 7/1,614,100 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
African / African-American	0.00801%	12,488

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: EFHC1
Protein: p.Pro13Ser
Coding: c.37C>T
MANE Select: NM_018100
dbSNP: rs754282571
Type: single nucleotide variant
Location: chr6:52420447 (GRCh38)
Gene constraint: LOEUF 0.906 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.31 · 2 PDB
Residue 13: the 'required for its localization in the mitotic spindle and interaction with alpha-tubulin' region

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-pro13ser (accessed [today's date]).

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