Is CD58 p.Phe77Leu (c.229T>C) pathogenic?

CD58 p.Phe77Leu (c.229T>C) is classified Uncertain significance in CD58 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-12). AlphaMissense: likely pathogenic (0.9353); Absent from gnomAD v4.1.

How common is CD58 p.Phe77Leu (c.229T>C) in the general population?

CD58 p.Phe77Leu (c.229T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CD58 p.Phe77Leu (c.229T>C)?

AlphaMissense predicts likely pathogenic (score 0.9353) — an in-silico prediction, not a clinical call.

CD58 p.Phe77Leu

c.229T>C · VCV3998295

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9353 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9353	likely pathogenic · top 3% in CD58
REVEL	0.103	moderately benign-leaning
SaProt	LLR -9.20	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.2	GERP 0.1, phastCons 0.066
Regional constraint	o/e 0.89	unconstrained · MANE · 56 kb · p 0.052 · regional, not allelic
Overall
CADD	18.35	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

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.Phe77Leu
Coding: c.229T>C
MANE Select: NM_001779
Type: single nucleotide variant
Location: chr1:116544446 (GRCh38)
Gene constraint: LOEUF 0.756 · pLI 0.35 (gnomAD)
Structure: AlphaFold pLDDT 83.54 · 3 PDB
Residue 77: an α-helix; 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-phe77leu (accessed [today's date]).

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