Is CRYAA p.Asp24Asn (c.70G>A) pathogenic?

CRYAA p.Asp24Asn (c.70G>A) is classified Uncertain significance in CRYAA (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-22). AlphaMissense: likely pathogenic (0.8549); Very rare (popmax 0.00291%, afr).

How common is CRYAA p.Asp24Asn (c.70G>A) in the general population?

CRYAA p.Asp24Asn (c.70G>A) is very rare (popmax 0.00291%, afr) (gnomAD).

What do computational predictors say about CRYAA p.Asp24Asn (c.70G>A)?

AlphaMissense predicts likely pathogenic (score 0.8549) — an in-silico prediction, not a clinical call.

CRYAA p.Asp24Asn

c.70G>A · rs756926049 · VCV3077700

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8549 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00291%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8549	likely pathogenic
REVEL	0.754	pathogenic-leaning
SaProt	LLR -9.54	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 4.7, phastCons 1
Regional constraint	o/e 0.13	constrained · MANE · 3,177 bp · p 1.9e-11 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00291% African / African-American · 1/34,338 alleles

Filtering AF 0.000112% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.1e-05%

Overall 0.000636% 6/943,232 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00291%	34,338
Remaining individualsnot grpmax-eligible	0.00236%	42,392
South Asian	0.00126%	79,544
European (non-Finnish)	0.000419%	238,395

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: CRYAA
Protein: p.Asp24Asn
Coding: c.70G>A
MANE Select: NM_000394
dbSNP: rs756926049
Type: single nucleotide variant
Location: chr21:43169169 (GRCh38)
Structure: AlphaFold pLDDT 74.60 · 5 PDB
Residue 24: a UniProt-annotated variant site (in ctrct9; uncertain significance); the 'required for complex formation with bfsp1 and bfsp2; during homooligomerization, mediates the association of 2 dimers to form a tetramer' region

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

Similar variants

CRYAA p.Arg116Cys Pathogenic ★★ same type
CRYAA p.Arg116His Pathogenic ★★ same type
CRYAA p.Arg116Ser Pathogenic ★★ same type
CRYAA p.Arg12Cys Pathogenic/Likely pathogenic ★★ same type
CRYAA p.Arg21Gln Pathogenic ★★ ⚠ same type
CRYAA p.Arg21Trp Pathogenic/Likely pathogenic ★★ same type
CRYAA p.Arg54Cys Pathogenic/Likely pathogenic ★★ same type
CRYAA p.Gly98Arg 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/cryaa-p-asp24asn (accessed [today's date]).

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