Is CRYAB p.Phe14= (c.42C>T) pathogenic?

CRYAB p.Phe14= (c.42C>T) is classified Likely benign in CRYAB (ClinVar, Single submitter, 1 submitter; last evaluated 2015-07-23). Very rare (popmax 0.00224%, eas).

How common is CRYAB p.Phe14= (c.42C>T) in the general population?

CRYAB p.Phe14= (c.42C>T) is very rare (popmax 0.00224%, eas) (gnomAD).

CRYAB p.Phe14=

c.42C>T · rs876657445 · VCV227276

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00224%, eas)

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 1.5	GERP -3.1, phastCons 1
Overall
CADD	10.75	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00224% East Asian · 1/44,590 alleles

Overall 0.000138% 2/1,452,180 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00224%	44,590
South Asian	0.00112%	89,218

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.Phe14=
Coding: c.42C>T
MANE Select: NM_001289808
dbSNP: rs876657445
Type: single nucleotide variant
Location: chr11:111911683 (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

Similar variants

CRYAB p.Phe14Ser Uncertain significance ★★ same residue
CRYAB p.Phe14Val Uncertain significance ★ ⚠ same residue
CRYAB c.324+4T>A Uncertain significance ★★ same type
CRYAB c.324+5G>T Uncertain significance ★★ same type
CRYAB c.325-1G>A Uncertain significance ★★ same type
CRYAB c.325-2A>G Uncertain significance ★★ same type
CRYAB c.-5C>T Uncertain significance ★★ same type
CRYAB p.Ala168Gly Uncertain significance ★★ ⚠ 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/cryab-p-phe14 (accessed [today's date]).

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