Is CD5 p.Asn241Lys (c.723C>G) pathogenic?

CD5 p.Asn241Lys (c.723C>G) is classified Uncertain significance in CD5 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-12). AlphaMissense: ambiguous (0.5416); Ultra-rare (popmax 0.0241%, nfe).

How common is CD5 p.Asn241Lys (c.723C>G) in the general population?

CD5 p.Asn241Lys (c.723C>G) is ultra-rare (popmax 0.0241%, nfe) (gnomAD).

What do computational predictors say about CD5 p.Asn241Lys (c.723C>G)?

AlphaMissense predicts ambiguous (score 0.5416) — an in-silico prediction, not a clinical call.

CD5 p.Asn241Lys

c.723C>G · rs199815445 · VCV2410091

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5416 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0241%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5416	ambiguous
REVEL	0.096	moderately benign-leaning
SaProt	LLR -8.54	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 -2.4	GERP -3.2
Regional constraint	o/e 0.86	unconstrained · MANE · 23 kb · p 0.00031 · regional, not allelic
Overall
CADD	0.628	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 0.0241% European (non-Finnish) · 284/1,180,054 alleles

Filtering AF 0.0217% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0208%

Overall 0.02% 323/1,614,076 alleles · ultra-rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0368%	2,717
European (non-Finnish)grpmax	0.0241%	4,155
South Asian	0.0121%	8,281
Admixed American	0.005%	20,004
African / African-American	0.00267%	37,472

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: CD5
Protein: p.Asn241Lys
Coding: c.723C>G
MANE Select: NM_014207
dbSNP: rs199815445
Type: single nucleotide variant
Location: chr11:61119493 (GRCh38)
Gene constraint: LOEUF 0.835 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.32 · 4 PDB
Residue 241: a disulfide bond; the srcr 2 domain

Full CD5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CD5 p.Ala471Val Benign ★★ same type
CD5 p.Pro224Leu Benign ★★ same type
CD5 p.Ala295Ser Uncertain significance ★ ⚠ same type
CD5 p.Ala492Asp Uncertain significance ★ ⚠ same type
CD5 p.Ala492Val Uncertain significance ★ ⚠ same type
CD5 p.Ala77Val Uncertain significance ★ ⚠ same type
CD5 p.Arg228Gln Uncertain significance ★ ⚠ same type
CD5 p.Arg338Gln 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/cd5-p-asn241lys (accessed [today's date]).

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