Is CRYBA1 p.Asn155Ser (c.464A>G) pathogenic?

CRYBA1 p.Asn155Ser (c.464A>G) is classified Conflicting classifications of pathogenicity in CRYBA1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2022-11-21). AlphaMissense: likely benign (0.0628); Ultra-rare (popmax 0.0934%, afr); Associated with Inborn genetic diseases.

What condition is associated with CRYBA1 p.Asn155Ser (c.464A>G)?

CRYBA1 p.Asn155Ser (c.464A>G) is associated with Inborn genetic diseases, cataract 10 multiple types (ClinVar).

How common is CRYBA1 p.Asn155Ser (c.464A>G) in the general population?

CRYBA1 p.Asn155Ser (c.464A>G) is ultra-rare (popmax 0.0934%, afr) (gnomAD).

What do computational predictors say about CRYBA1 p.Asn155Ser (c.464A>G)?

AlphaMissense predicts likely benign (score 0.0628) — an in-silico prediction, not a clinical call.

CRYBA1 p.Asn155Ser

c.464A>G · rs140057151 · VCV1126851

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0628 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0934%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0628	likely benign
REVEL	0.172	moderately benign-leaning
SaProt	LLR -6.08	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 6.2	GERP -0.31, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 7,482 bp · p 0.0017 · regional, not allelic
Overall
CADD	15.18	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 0.0934% African / African-American · 70/74,938 alleles

Filtering AF 0.0757% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0693%

Overall 0.00465% 75/1,614,110 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0934%	1,071
Remaining individualsnot grpmax-eligible	0.0064%	15,622
European (non-Finnish)	8.47e-05%	1,180,054

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: CRYBA1
Protein: p.Asn155Ser
Coding: c.464A>G
MANE Select: NM_005208
dbSNP: rs140057151
Type: single nucleotide variant
Location: chr17:29253746 (GRCh38)
Gene constraint: LOEUF 0.987 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 88.27
Residue 155: the beta/gamma crystallin 'greek key' 3 domain

Full CRYBA1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: cataract 10 multiple types

Similar variants

CRYBA1 p.Asn155Lys Uncertain significance ★ ⚠ same residue
CRYBA1 c.215+1G>A Pathogenic/Likely pathogenic ★★ same condition
CRYBA1 c.215+1G>T Pathogenic/Likely pathogenic ★★ same condition
CRYBA1 c.500+1G>A Likely pathogenic ★★ same condition
CRYBA1 p.Arg109His Uncertain significance ★★ ⚠ same condition
CRYBA1 p.Glu39Asp Uncertain significance ★★ ⚠ same condition
CRYBA1 p.Leu183Ter Uncertain significance ★★ same condition
CRYBA1 c.215+16C>T Benign ★★ 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/cryba1-p-asn155ser (accessed [today's date]).

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