Is CRYL1 p.Ser67Arg (c.199A>C) pathogenic?

CRYL1 p.Ser67Arg (c.199A>C) is classified Uncertain significance in CRYL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-20). AlphaMissense: likely benign (0.2711); Absent from gnomAD v4.1.

How common is CRYL1 p.Ser67Arg (c.199A>C) in the general population?

CRYL1 p.Ser67Arg (c.199A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CRYL1 p.Ser67Arg (c.199A>C)?

AlphaMissense predicts likely benign (score 0.2711) — an in-silico prediction, not a clinical call.

CRYL1 p.Ser67Arg

c.199A>C · VCV3497468

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2711 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2711	likely benign
REVEL	0.185	benign-leaning
SaProt	LLR -7.03	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.56	GERP -1.2, phastCons 0.026
Regional constraint	o/e 1.01	unconstrained · MANE · 122 kb · p 0.88 · regional, not allelic
Overall
CADD	11.98	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CRYL1
Protein: p.Ser67Arg
Coding: c.199A>C
MANE Select: NM_015974
Type: single nucleotide variant
Location: chr13:20489447 (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 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
CRYL1 c.846+110A>G 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-ser67arg (accessed [today's date]).

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