Is BTD p.Ala22Pro (c.64G>C) pathogenic?

BTD p.Ala22Pro (c.64G>C) is classified Uncertain significance in BTD (ClinVar, Single submitter, 1 submitter; last evaluated 2021-01-12). AlphaMissense: likely benign (0.0953); Absent from gnomAD v4.1.

How common is BTD p.Ala22Pro (c.64G>C) in the general population?

BTD p.Ala22Pro (c.64G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BTD p.Ala22Pro (c.64G>C)?

AlphaMissense predicts likely benign (score 0.0953) — an in-silico prediction, not a clinical call.

BTD p.Ala22Pro

c.64G>C · rs761112772 · VCV1330058

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0953 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0953	likely benign
REVEL	0.462	indeterminate
SaProt	LLR -8.62	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2	GERP 0.39, phastCons 0.07
Regional constraint	o/e 1.04	unconstrained · MANE · 10 kb · p 0.35 · regional, not allelic
Overall
CADD	17.09	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM A42P vs ClinVar A22P) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BTD
Protein: p.Ala22Pro
Coding: c.64G>C
MANE Select: NM_001370658
dbSNP: rs761112772
Type: single nucleotide variant
Location: chr3:15635503 (GRCh38)
Gene constraint: LOEUF 1.22 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.77

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

Similar variants

BTD c.1330G>C Pathogenic ★★ same type
BTD c.249+1G>T Likely pathogenic ★★ same type
BTD c.400-2A>G Likely pathogenic ★★ same type
BTD c.-17+2T>C Pathogenic/Likely pathogenic ★★ same type
BTD p.Ala142Val Pathogenic/Likely pathogenic ★★ same type
BTD p.Ala217Thr Pathogenic/Likely pathogenic ★★ ⚠ same type
BTD p.Ala269Val Pathogenic/Likely pathogenic ★★ same type
BTD p.Ala279Pro Pathogenic/Likely pathogenic ★★ 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/btd-p-ala22pro (accessed [today's date]).

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