Is CRYM p.Ser160Phe (c.479C>T) pathogenic?

CRYM p.Ser160Phe (c.479C>T) is classified Uncertain significance in CRYM (ClinVar, Single submitter, 1 submitter; last evaluated 2018-05-15). AlphaMissense: likely benign (0.1587); Very rare (popmax 0.00299%, afr).

How common is CRYM p.Ser160Phe (c.479C>T) in the general population?

CRYM p.Ser160Phe (c.479C>T) is very rare (popmax 0.00299%, afr) (gnomAD).

What do computational predictors say about CRYM p.Ser160Phe (c.479C>T)?

AlphaMissense predicts likely benign (score 0.1587) — an in-silico prediction, not a clinical call.

CRYM p.Ser160Phe

c.479C>T · rs774967684 · VCV546159

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1587 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00299%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1587	likely benign
REVEL	0.365	indeterminate
SaProt	LLR -9.74	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.1	GERP 1.8, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 19 kb · p 0.0044 · regional, not allelic
Overall
CADD	22.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00299% African / African-American · 2/66,956 alleles

Filtering AF 0.000496% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000186%

Overall 0.000506% 7/1,383,144 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00299%	33,478
European (non-Finnish)	0.00051%	196,046

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.Ser160Phe
Coding: c.479C>T
MANE Select: NM_001376256
dbSNP: rs774967684
Type: single nucleotide variant
Location: chr16:21269800 (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.Ser160= Likely benign ★ same residue
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

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-ser160phe (accessed [today's date]).

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