Is BPHL p.Arg231Gln (c.692G>A) pathogenic?

BPHL p.Arg231Gln (c.692G>A) is classified Likely benign in BPHL (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-07). AlphaMissense: likely benign (0.0704); Very rare (popmax 0.00667%, amr).

How common is BPHL p.Arg231Gln (c.692G>A) in the general population?

BPHL p.Arg231Gln (c.692G>A) is very rare (popmax 0.00667%, amr) (gnomAD).

What do computational predictors say about BPHL p.Arg231Gln (c.692G>A)?

AlphaMissense predicts likely benign (score 0.0704) — an in-silico prediction, not a clinical call.

BPHL p.Arg231Gln

c.692G>A · rs762056309 · VCV2515135

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0704 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00667%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0704	likely benign
REVEL	0.092	moderately benign-leaning
SaProt	LLR -2.09	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.22	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 0.65	GERP -2, phastCons 0.87
Regional constraint	o/e 0.95	unconstrained · MANE · 34 kb · p 0.31 · regional, not allelic
Overall
CADD	12.96	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 0.00667% Admixed American · 4/59,994 alleles

Filtering AF 0.00286% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00195%

Overall 0.00143% 23/1,614,006 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00667%	14,999
South Asian	0.00659%	15,180
Finnishnot grpmax-eligible	0.00625%	16,003
African / African-American	0.00134%	74,904
European (non-Finnish)	0.000678%	147,504

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: BPHL
Protein: p.Arg231Gln
Coding: c.692G>A
MANE Select: NM_004332
dbSNP: rs762056309
Type: single nucleotide variant
Location: chr6:3140413 (GRCh38)
Gene constraint: LOEUF 1.262 · pLI <0.01 · ClinGen HI dosage-sensitivity unlikely (gnomAD)
Structure: AlphaFold pLDDT 92.43 · 4 PDB
Residue 231: an α-helix

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

Similar variants

TUBB2A p.Thr178Met Pathogenic/Likely pathogenic ★★ same type
BPHL p.Ala164Pro Uncertain significance ★ ⚠ same type
BPHL p.Ala164Thr Uncertain significance ★ ⚠ same type
BPHL p.Ala166Thr Uncertain significance ★ ⚠ same type
BPHL p.Ala236Ser Uncertain significance ★ ⚠ same type
BPHL p.Ala252Val Uncertain significance ★ ⚠ same type
BPHL p.Ala34Ser Uncertain significance ★ ⚠ same type
BPHL p.Arg12Cys 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/bphl-p-arg231gln (accessed [today's date]).

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