Is CRYAB p.Asp2= (c.6C>T) pathogenic?

CRYAB p.Asp2= (c.6C>T) is classified Likely benign in CRYAB (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-09-24). Very rare (popmax 0.00268%, afr); Associated with Cardiovascular phenotype.

What condition is associated with CRYAB p.Asp2= (c.6C>T)?

CRYAB p.Asp2= (c.6C>T) is associated with Cardiovascular phenotype (ClinVar).

How common is CRYAB p.Asp2= (c.6C>T) in the general population?

CRYAB p.Asp2= (c.6C>T) is very rare (popmax 0.00268%, afr) (gnomAD).

CRYAB p.Asp2=

c.6C>T · rs782577028 · VCV516018

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00268%, 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 5.8	GERP 1.2, phastCons 1
Overall
CADD	11.31	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00268% African / African-American · 2/74,508 alleles

Filtering AF 0.000445% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000167%

Overall 0.000126% 2/1,582,510 alleles · very rare exomes 1/1,430,290 · genomes 1/152,220 · joint denominator

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.Asp2=
Coding: c.6C>T
MANE Select: NM_001289808
dbSNP: rs782577028
Type: single nucleotide variant
Location: chr11:111911719 (GRCh38)
Gene constraint: LOEUF 1.18 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.42 · 21 PDB

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

Similar variants

CRYAB p.Asp2Asn Uncertain significance ★★ ⚠ same residue
CRYAB c.324+4T>A Uncertain significance ★★ same condition
CRYAB c.325-2A>G Uncertain significance ★★ same condition
CRYAB c.-5C>T Uncertain significance ★★ same condition
CRYAB p.Ala171Thr Uncertain significance ★★ ⚠ same condition
CRYAB p.Arg11Cys Uncertain significance ★★ ⚠ same condition
CRYAB p.Arg123Gln Uncertain significance ★★ ⚠ same condition
CRYAB p.Arg157Cys 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-asp2 (accessed [today's date]).

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