Is BAHD1 p.Arg577His (c.1730G>A) pathogenic?

BAHD1 p.Arg577His (c.1730G>A) is classified Uncertain significance in BAHD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-26). AlphaMissense: likely benign (0.2161); Very rare (popmax 0.00267%, afr).

How common is BAHD1 p.Arg577His (c.1730G>A) in the general population?

BAHD1 p.Arg577His (c.1730G>A) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about BAHD1 p.Arg577His (c.1730G>A)?

AlphaMissense predicts likely benign (score 0.2161) — an in-silico prediction, not a clinical call.

BAHD1 p.Arg577His

c.1730G>A · rs563191486 · VCV2467924

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2161 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2161	likely benign
REVEL	0.077	moderately benign-leaning
SaProt	LLR -8.25	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 12	GERP 1.6, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 3,779 bp · p 0.57 · regional, not allelic
Overall
CADD	26.5	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 0.00267% African / African-American · 2/75,020 alleles

Filtering AF 0.00145% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00123%

Overall 0.00186% 30/1,611,856 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,554
African / African-Americangrpmax	0.00267%	37,510
European (non-Finnish)	0.00212%	47,175
Remaining individualsnot grpmax-eligible	0.0016%	62,456
South Asian	0.0011%	91,014

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg577His
Coding: c.1730G>A
MANE Select: NM_014952
dbSNP: rs563191486
Type: single nucleotide variant
Location: chr15:40462209 (GRCh38)
Gene constraint: LOEUF 0.447 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 51.19
Residue 577: 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-arg577his (accessed [today's date]).

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