Is CRYGB p.Ser104= (c.312A>G) pathogenic?

CRYGB p.Ser104= (c.312A>G) is classified Benign in CRYGB (ClinVar, Single submitter, 2 submitters; last evaluated 2024-12-18). Low-frequency (popmax 2.57%, sas); Associated with cataract 39 multiple types.

What condition is associated with CRYGB p.Ser104= (c.312A>G)?

CRYGB p.Ser104= (c.312A>G) is associated with cataract 39 multiple types (ClinVar).

How common is CRYGB p.Ser104= (c.312A>G) in the general population?

CRYGB p.Ser104= (c.312A>G) is low-frequency (popmax 2.57%, sas) (gnomAD).

How is Early onset non-syndromic cataract inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

CRYGB p.Ser104=

c.312A>G · rs200750137 · VCV474172

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.57%, sas)

Conditions

cataract 39 multiple types

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 -2.1	GERP -4.7
Overall
CADD	6.143	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.57% South Asian · 2,337/91,028 alleles

Filtering AF 2.48% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.45%

Overall 0.155% 2,497/1,614,066 alleles · low-frequency exomes 2,380/1,461,728 · genomes 117/152,338 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	2.57%	39
Middle Eastern	0.182%	550
Remaining individualsnot grpmax-eligible	0.158%	631
East Asian	0.00891%	11,223
European (non-Finnish)	0.00373%	26,818
Admixed American	0.00333%	30,004

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: CRYGB
Protein: p.Ser104=
Coding: c.312A>G
MANE Select: NM_005210
dbSNP: rs200750137
Type: single nucleotide variant
Location: chr2:208142854 (GRCh38)
Gene constraint: LOEUF 1.305 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.86 · 2 PDB
Residue 104: a β-strand; the beta/gamma crystallin 'greek key' 3 domain

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

Disease context

cataract 39 multiple types — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Early onset non-syndromic cataract (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Infancy, Neonatal

Similar variants

CRYGB p.Ala160Pro Uncertain significance ★★ ⚠ same condition
CRYGB p.Arg116His Uncertain significance ★★ ⚠ same condition
CRYGB p.Asp95Asn Uncertain significance ★★ ⚠ same condition
CRYGB p.Ile82Val Uncertain significance ★★ ⚠ same condition
CRYGB p.Pro84Leu Uncertain significance ★★ ⚠ same condition
CRYGB p.Ser16Asn Uncertain significance ★★ ⚠ same condition
CRYGB p.Arg59Trp Benign ★★ same condition
CRYGB p.Ile111Leu 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/crygb-p-ser104 (accessed [today's date]).

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