Is CRYM p.Phe269= (c.807T>C) pathogenic?

CRYM p.Phe269= (c.807T>C) is classified Benign/Likely benign in CRYM (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-04-01). Rare (popmax 0.608%, nfe).

How common is CRYM p.Phe269= (c.807T>C) in the general population?

CRYM p.Phe269= (c.807T>C) is rare (popmax 0.608%, nfe) (gnomAD).

CRYM p.Phe269=

c.807T>C · rs144588424 · VCV178330

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

rare (popmax 0.608%, nfe)

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 -4.7	GERP -4.1
Overall
CADD	1.123	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.608% European (non-Finnish) · 7,178/1,179,972 alleles

Filtering AF 0.597% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.592%

Overall 0.523% 8,436/1,614,054 alleles · rare exomes 7,849/1,461,812 · genomes 587/152,242 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.917%	109
European (non-Finnish)grpmax	0.608%	164
Remaining individualsnot grpmax-eligible	0.394%	254
Admixed American	0.307%	326
Ashkenazi Jewishnot grpmax-eligible	0.274%	366
Middle Eastern	0.198%	505
South Asian	0.103%	969
African / African-American	0.0706%	1,416
East Asian	0.00223%	44,876

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: CRYM
Protein: p.Phe269=
Coding: c.807T>C
MANE Select: NM_001376256
dbSNP: rs144588424
Type: single nucleotide variant
Location: chr16:21261327 (GRCh38)
Gene constraint: LOEUF 0.841 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.06 · 1 PDB

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

Similar variants

CRYM p.Ala178Glu Uncertain significance ★★ ⚠ same type
CRYM p.Glu172Gly Uncertain significance ★★ ⚠ same type
CRYM p.Leu72Val Uncertain significance ★★ ⚠ same type
CRYM p.Met295Ile Uncertain significance ★★ ⚠ same type
CRYM p.Thr95Ser Uncertain significance ★★ ⚠ same type
CRYM p.Val4Leu Uncertain significance ★★ ⚠ same type
CRYM c.171-118C>T Benign ★★ same type
CRYM c.171-19G>A Likely benign ★★ 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/crym-p-phe269 (accessed [today's date]).

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