Is CD58 p.Arg246Gly (c.736A>G) pathogenic?

CD58 p.Arg246Gly (c.736A>G) is classified Uncertain significance in CD58 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-06). AlphaMissense: likely benign (0.0982); Absent from gnomAD v4.1.

How common is CD58 p.Arg246Gly (c.736A>G) in the general population?

CD58 p.Arg246Gly (c.736A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CD58 p.Arg246Gly (c.736A>G)?

AlphaMissense predicts likely benign (score 0.0982) — an in-silico prediction, not a clinical call.

CD58 p.Arg246Gly

c.736A>G · rs2526148843 · VCV2474344

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0982 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0982	likely benign
REVEL	0.088	moderately benign-leaning
SaProt	LLR -6.71	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 -8	GERP -1.7
Regional constraint	o/e 0.89	unconstrained · MANE · 56 kb · p 0.052 · regional, not allelic
Overall
CADD	12.6	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: CD58
Protein: p.Arg246Gly
Coding: c.736A>G
MANE Select: NM_001779
dbSNP: rs2526148843
Type: single nucleotide variant
Location: chr1:116519238 (GRCh38)
Gene constraint: LOEUF 0.756 · pLI 0.35 (gnomAD)
Structure: AlphaFold pLDDT 83.54 · 3 PDB

Full CD58 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CD58 p.Ala224Ser Uncertain significance ★ ⚠ same type
CD58 p.Ala7Glu Uncertain significance ★ ⚠ same type
CD58 p.Arg168Pro Uncertain significance ★ ⚠ same type
CD58 p.Asn135Thr Uncertain significance ★ ⚠ same type
CD58 p.Asn179Asp Uncertain significance ★ ⚠ same type
CD58 p.Asn48Asp Uncertain significance ★ ⚠ same type
CD58 p.Cys229Tyr Uncertain significance ★ ⚠ same type
CD58 p.Gln31His 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/cd58-p-arg246gly (accessed [today's date]).

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