Is CRYAB p.Lys72= (c.216G>A) pathogenic?

CRYAB p.Lys72= (c.216G>A) is classified Benign/Likely benign in CRYAB (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-06). Ultra-rare (popmax 0.032%, afr); Associated with Cardiovascular phenotype.

What condition is associated with CRYAB p.Lys72= (c.216G>A)?

CRYAB p.Lys72= (c.216G>A) is associated with Cardiovascular phenotype, dilated cardiomyopathy 1II (ClinVar).

How common is CRYAB p.Lys72= (c.216G>A) in the general population?

CRYAB p.Lys72= (c.216G>A) is ultra-rare (popmax 0.032%, afr) (gnomAD).

CRYAB p.Lys72=

c.216G>A · rs561116151 · VCV477732

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.032%, afr)

Conditions

Cardiovascular phenotype

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 1.4	GERP 1.6, phastCons 1
Overall
CADD	10.96	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.032% African / African-American · 24/75,038 alleles

Filtering AF 0.022% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0187%

Overall 0.00396% 64/1,614,126 alleles · ultra-rare exomes 54/1,461,874 · genomes 10/152,252 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.032%	3,127
European (non-Finnish)	0.00322%	31,053
Remaining individualsnot grpmax-eligible	0.0032%	31,256

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: CRYAB
Protein: p.Lys72=
Coding: c.216G>A
MANE Select: NM_001289808
dbSNP: rs561116151
Type: single nucleotide variant
Location: chr11:111910435 (GRCh38)
Gene constraint: LOEUF 1.18 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.42 · 21 PDB
Residue 72: the shsp domain; a β-strand

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

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: dilated cardiomyopathy 1II

Similar variants

CRYAB p.Lys72Met Uncertain significance ★ ⚠ same residue
CRYAB c.324+4T>A Uncertain significance ★★ same condition
CRYAB c.324+5G>T Uncertain significance ★★ same condition
CRYAB c.325-1G>A Uncertain significance ★★ same condition
CRYAB c.325-2A>G Uncertain significance ★★ same condition
CRYAB c.-5C>T Uncertain significance ★★ same condition
CRYAB p.Ala168Gly Uncertain significance ★★ ⚠ same condition
CRYAB p.Ala171Thr Uncertain significance ★★ ⚠ same condition

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/cryab-p-lys72 (accessed [today's date]).

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