Is CRYL1 p.Arg171Ser (c.513A>T) pathogenic?

CRYL1 p.Arg171Ser (c.513A>T) is classified Uncertain significance in CRYL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-14). AlphaMissense: likely benign (0.3225); Ultra-rare (popmax 0.0574%, afr).

How common is CRYL1 p.Arg171Ser (c.513A>T) in the general population?

CRYL1 p.Arg171Ser (c.513A>T) is ultra-rare (popmax 0.0574%, afr) (gnomAD).

What do computational predictors say about CRYL1 p.Arg171Ser (c.513A>T)?

AlphaMissense predicts likely benign (score 0.3225) — an in-silico prediction, not a clinical call.

CRYL1 p.Arg171Ser

c.513A>T · rs201065581 · VCV3077919

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3225 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0574%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.3225	likely benign
REVEL	0.429	indeterminate
SaProt	LLR -6.15	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 -0.32	GERP -4.6, phastCons 0.28
Regional constraint	o/e 1.01	unconstrained · MANE · 122 kb · p 0.88 · regional, not allelic
Overall
CADD	21.2	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 0.0574% African / African-American · 43/74,918 alleles

Filtering AF 0.0437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.039%

Overall 0.00279% 45/1,613,798 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0574%	1,742
Admixed American	0.00167%	59,938
Remaining individualsnot grpmax-eligible	0.0016%	62,488

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.Arg171Ser
Coding: c.513A>T
MANE Select: NM_015974
dbSNP: rs201065581
Type: single nucleotide variant
Location: chr13:20432222 (GRCh38)
Gene constraint: LOEUF 1.297 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.66 · 1 PDB
Residue 171: an α-helix

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

Similar variants

CRYL1 p.Arg171Ile 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-arg171ser (accessed [today's date]).

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