Is CD58 p.Gln31His (c.93A>C) pathogenic?

CD58 p.Gln31His (c.93A>C) is classified Uncertain significance in CD58 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-20). AlphaMissense: likely benign (0.2204); Very rare (popmax 0.00249%, nfe).

How common is CD58 p.Gln31His (c.93A>C) in the general population?

CD58 p.Gln31His (c.93A>C) is very rare (popmax 0.00249%, nfe) (gnomAD).

What do computational predictors say about CD58 p.Gln31His (c.93A>C)?

AlphaMissense predicts likely benign (score 0.2204) — an in-silico prediction, not a clinical call.

CD58 p.Gln31His

c.93A>C · VCV3488124

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2204 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00249%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2204	likely benign
REVEL	0.14	moderately benign-leaning
SaProt	LLR -9.19	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 -3.7	GERP -2.8
Regional constraint	o/e 0.89	unconstrained · MANE · 56 kb · p 0.052 · regional, not allelic
Overall
CADD	0.448	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 0.00249% European (non-Finnish) · 29/1,166,836 alleles

Filtering AF 0.00174% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00151%

Overall 0.00189% 30/1,585,394 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00249%	40,236
Remaining individualsnot grpmax-eligible	0.00163%	61,256

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: CD58
Protein: p.Gln31His
Coding: c.93A>C
MANE Select: NM_001779
Type: single nucleotide variant
Location: chr1:116544582 (GRCh38)
Gene constraint: LOEUF 0.756 · pLI 0.35 (gnomAD)
Structure: AlphaFold pLDDT 83.54 · 3 PDB
Residue 31: a β-strand; the ig-like domain

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.Arg246Gly 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

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-gln31his (accessed [today's date]).

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