Is BAD p.Ser134Thr (c.401G>C) pathogenic?

BAD p.Ser134Thr (c.401G>C) is classified Uncertain significance in BAD (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-21). AlphaMissense: likely benign (0.3228); Ultra-rare (popmax 0.0171%, mid).

How common is BAD p.Ser134Thr (c.401G>C) in the general population?

BAD p.Ser134Thr (c.401G>C) is ultra-rare (popmax 0.0171%, mid) (gnomAD).

What do computational predictors say about BAD p.Ser134Thr (c.401G>C)?

AlphaMissense predicts likely benign (score 0.3228) — an in-silico prediction, not a clinical call.

BAD p.Ser134Thr

c.401G>C · VCV3816906

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3228 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0171%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3228	likely benign
REVEL	0.259	benign-leaning
SaProt	LLR -7.01	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 7.6	GERP 1.7, phastCons 1
Regional constraint	o/e 1.23	unconstrained · MANE · 14 kb · p 0.0004 · regional, not allelic
Overall
CADD	27.0	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 0.0171% Middle Eastern · 1/5,832 alleles

Filtering AF 0.000127% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.3e-05%

Overall 0.000636% 9/1,414,868 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0171%	5,832
Remaining individualsnot grpmax-eligible	0.00332%	30,164
South Asian	0.00116%	86,506
European (non-Finnish)	0.000434%	230,229

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: BAD
Protein: p.Ser134Thr
Coding: c.401G>C
MANE Select: NM_032989
Type: single nucleotide variant
Location: chr11:64270315 (GRCh38)
Gene constraint: LOEUF 1.889 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.91 · 6 PDB
Residue 134: a modified residue (phosphoserine); the 'disordered' region

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

Similar variants

BAD p.Ala106Val Uncertain significance ★ ⚠ same type
BAD p.Ala138Thr Uncertain significance ★ ⚠ same type
BAD p.Ala41Thr Uncertain significance ★ ⚠ same type
BAD p.Arg116Ser Uncertain significance ★ ⚠ same type
BAD p.Arg161Gly Uncertain significance ★ ⚠ same type
BAD p.Asp82Asn Uncertain significance ★ ⚠ same type
BAD p.Gln152Arg Uncertain significance ★ ⚠ same type
BAD p.Glu81Gln 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/bad-p-ser134thr (accessed [today's date]).

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