Is BAHD1 p.Pro240Ala (c.718C>G) pathogenic?

BAHD1 p.Pro240Ala (c.718C>G) is classified Uncertain significance in BAHD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-15). AlphaMissense: likely benign (0.0492); Ultra-rare (popmax 0.0879%, afr).

How common is BAHD1 p.Pro240Ala (c.718C>G) in the general population?

BAHD1 p.Pro240Ala (c.718C>G) is ultra-rare (popmax 0.0879%, afr) (gnomAD).

What do computational predictors say about BAHD1 p.Pro240Ala (c.718C>G)?

AlphaMissense predicts likely benign (score 0.0492) — an in-silico prediction, not a clinical call.

BAHD1 p.Pro240Ala

c.718C>G · rs137889089 · VCV3132853

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0492 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0879%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0492	likely benign
REVEL	0.072	moderately benign-leaning
SaProt	LLR -6.54	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 0.75	GERP -0.47
Regional constraint	o/e 0.98	unconstrained · MANE · 3,779 bp · p 0.57 · regional, not allelic
Overall
CADD	7.093	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 0.0879% African / African-American · 66/75,072 alleles

Filtering AF 0.0709% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0647%

Overall 0.00508% 82/1,612,814 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0879%	1,137
Middle Eastern	0.066%	1,515
Remaining individualsnot grpmax-eligible	0.0128%	7,807
East Asian	0.00223%	44,868
Admixed American	0.00167%	59,962
South Asian	0.0011%	91,036
European (non-Finnish)	8.48e-05%	1,179,697

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: BAHD1
Protein: p.Pro240Ala
Coding: c.718C>G
MANE Select: NM_014952
dbSNP: rs137889089
Type: single nucleotide variant
Location: chr15:40459182 (GRCh38)
Gene constraint: LOEUF 0.447 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 51.19
Residue 240: the 'disordered' region

Full BAHD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BAHD1 p.Gln298Lys Benign ★★ same type
BAHD1 p.Ala200Thr Uncertain significance ★ ⚠ same type
BAHD1 p.Ala264Thr Uncertain significance ★ ⚠ same type
BAHD1 p.Ala409Thr Uncertain significance ★ ⚠ same type
BAHD1 p.Ala409Val Uncertain significance ★ ⚠ same type
BAHD1 p.Ala418Pro Uncertain significance ★ ⚠ same type
BAHD1 p.Ala462Ser Uncertain significance ★ ⚠ same type
BAHD1 p.Ala462Thr 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/bahd1-p-pro240ala (accessed [today's date]).

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