Is CAPZB p.Thr164= (c.492C>T) pathogenic?

CAPZB p.Thr164= (c.492C>T) is classified Likely benign in CAPZB (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-01). Rare (popmax 0.485%, sas).

How common is CAPZB p.Thr164= (c.492C>T) in the general population?

CAPZB p.Thr164= (c.492C>T) is rare (popmax 0.485%, sas) (gnomAD).

CAPZB p.Thr164=

c.492C>T · rs373170769 · VCV2638431

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.485%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -7.4	GERP -3.5
Overall
CADD	3.383	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.485% South Asian · 442/91,074 alleles

Filtering AF 0.448% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.433%

Overall 0.0639% 1,031/1,613,552 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.485%	206
Middle Eastern	0.429%	233
Remaining individualsnot grpmax-eligible	0.0736%	1,358
European (non-Finnish)	0.0409%	2,447
Admixed American	0.035%	2,858
Finnishnot grpmax-eligible	0.0109%	9,143
East Asian	0.00668%	14,960
African / African-American	0.004%	25,013
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,602

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: CAPZB
Protein: p.Thr164=
Coding: c.492C>T
MANE Select: NM_004930
dbSNP: rs373170769
Type: single nucleotide variant
Location: chr1:19356731 (GRCh38)
Gene constraint: LOEUF 0.221 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 91.18 · 8 PDB
Residue 164: a β-strand

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

Similar variants

CAPZB p.Thr164Ile Uncertain significance ★ ⚠ same residue
CAPZB c.731+1496C>G Uncertain significance ★ ⚠ same type
CAPZB c.731+1519C>A Uncertain significance ★ same type
CAPZB c.731+1520A>G Uncertain significance ★ ⚠ same type
CAPZB c.731+1568G>A Uncertain significance ★ ⚠ same type
CAPZB p.Arg215His Uncertain significance ★ ⚠ same type
CAPZB p.Cys147Ser Uncertain significance ★ ⚠ same type
CAPZB p.Met88Val 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/capzb-p-thr164 (accessed [today's date]).

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