Is CD5L p.Cys191Arg (c.571T>C) pathogenic?

CD5L p.Cys191Arg (c.571T>C) is classified Uncertain significance in CD5L (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-26). AlphaMissense: ambiguous (0.3895); Very rare (popmax 0.00333%, amr).

How common is CD5L p.Cys191Arg (c.571T>C) in the general population?

CD5L p.Cys191Arg (c.571T>C) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about CD5L p.Cys191Arg (c.571T>C)?

AlphaMissense predicts ambiguous (score 0.3895) — an in-silico prediction, not a clinical call.

CD5L p.Cys191Arg

c.571T>C · rs1219792467 · VCV2303510

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3895 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3895	ambiguous
REVEL	0.156	moderately benign-leaning
SaProt	LLR -2.75	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.5, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 9,734 bp · p 0.89 · regional, not allelic
Overall
CADD	17.99	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 0.00333% Admixed American · 2/60,004 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000372% 6/1,614,038 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	30,002
European (non-Finnish)	0.000339%	295,010

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: CD5L
Protein: p.Cys191Arg
Coding: c.571T>C
MANE Select: NM_005894
dbSNP: rs1219792467
Type: single nucleotide variant
Location: chr1:157834554 (GRCh38)
Gene constraint: LOEUF 1.148 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.81 · 4 PDB
Residue 191: a disulfide bond; the srcr 2 domain

Full CD5L gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CD5L p.Ala172Ser Uncertain significance ★ ⚠ same type
CD5L p.Ala342Ser Uncertain significance ★ ⚠ same type
CD5L p.Ala59Val Uncertain significance ★ ⚠ same type
CD5L p.Arg150Leu Uncertain significance ★ same type
CD5L p.Arg198Leu Uncertain significance ★ ⚠ same type
CD5L p.Arg328Ile Uncertain significance ★ ⚠ same type
CD5L p.Asn272Ser Uncertain significance ★ ⚠ same type
CD5L p.Asn272Thr Uncertain significance ★ ⚠ 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/cd5l-p-cys191arg (accessed [today's date]).

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