Is CRYL1 p.Pro162Leu (c.485C>T) pathogenic?

CRYL1 p.Pro162Leu (c.485C>T) is classified Uncertain significance in CRYL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-12). AlphaMissense: likely benign (0.1107); Ultra-rare (popmax 0.0201%, eas).

How common is CRYL1 p.Pro162Leu (c.485C>T) in the general population?

CRYL1 p.Pro162Leu (c.485C>T) is ultra-rare (popmax 0.0201%, eas) (gnomAD).

What do computational predictors say about CRYL1 p.Pro162Leu (c.485C>T)?

AlphaMissense predicts likely benign (score 0.1107) — an in-silico prediction, not a clinical call.

CRYL1 p.Pro162Leu

c.485C>T · rs369439890 · VCV2593031

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1107 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0201%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1107	likely benign
REVEL	0.444	indeterminate
SaProt	LLR -11.47	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.3	GERP 2.6, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 122 kb · p 0.88 · regional, not allelic
Overall
CADD	28.1	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 0.0201% East Asian · 9/44,858 alleles

Filtering AF 0.0104% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00779%

Overall 0.00508% 82/1,613,484 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0201%	4,984
Middle Eastern	0.0164%	6,084
European (non-Finnish)	0.00568%	17,609
Remaining individualsnot grpmax-eligible	0.0048%	20,821
African / African-American	0.00134%	74,782
South Asian	0.0011%	91,058

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: CRYL1
Protein: p.Pro162Leu
Coding: c.485C>T
MANE Select: NM_015974
dbSNP: rs369439890
Type: single nucleotide variant
Location: chr13:20432250 (GRCh38)
Gene constraint: LOEUF 1.297 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.66 · 1 PDB

Full CRYL1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CRYL1 p.Pro162Arg Uncertain significance ★ ⚠ same residue
CRYL1 c.149+24A>G Benign ★★ same type
CRYL1 c.276+13C>T Benign ★★ same type
CRYL1 c.41+65T>G Benign ★★ same type
CRYL1 c.438+49G>T Benign ★★ same type
CRYL1 c.438+62C>T Benign ★★ same type
CRYL1 c.439-40A>G Benign ★★ same type
CRYL1 c.634-202T>C 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/cryl1-p-pro162leu (accessed [today's date]).

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