Is CD163 p.Cys355Phe (c.1064G>T) pathogenic?

CD163 p.Cys355Phe (c.1064G>T) is classified Uncertain significance in CD163 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-03). AlphaMissense: likely pathogenic (0.9767); Absent from gnomAD v4.1.

How common is CD163 p.Cys355Phe (c.1064G>T) in the general population?

CD163 p.Cys355Phe (c.1064G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CD163 p.Cys355Phe (c.1064G>T)?

AlphaMissense predicts likely pathogenic (score 0.9767) — an in-silico prediction, not a clinical call.

CD163 p.Cys355Phe

c.1064G>T · VCV3997990

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9767 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9767	likely pathogenic · top 2% in CD163
REVEL	0.499	indeterminate
SaProt	LLR -15.75	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 0.93, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 24 kb · p 1.4e-17 · regional, not allelic
Overall
CADD	28.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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: CD163
Protein: p.Cys355Phe
Coding: c.1064G>T
MANE Select: NM_203416
Type: single nucleotide variant
Location: chr12:7496848 (GRCh38)
Gene constraint: LOEUF 0.56 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.72 · 14 PDB
Residue 355: a disulfide bond; the srcr 3 domain

Full CD163 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CD163 c.3344-24C>A Benign ★★ same type
CD163 c.3344-56G>A Likely benign ★★ same type
CD163 c.457+9T>A Benign ★★ same type
CD163 p.Asn642Lys Benign ★★ same type
CD163 p.Asn892= Benign ★★ same type
CD163 p.Cys1008= Benign ★★ same type
CD163 p.Ile342Val Benign ★★ same type
CD163 p.Leu867= Benign ★★ 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/cd163-p-cys355phe (accessed [today's date]).

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