Is CD163 p.Asp129Gly (c.386A>G) pathogenic?

CD163 p.Asp129Gly (c.386A>G) is classified Uncertain significance in CD163 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-20). AlphaMissense: likely benign (0.2382); Ultra-rare (popmax 0.0103%, nfe).

How common is CD163 p.Asp129Gly (c.386A>G) in the general population?

CD163 p.Asp129Gly (c.386A>G) is ultra-rare (popmax 0.0103%, nfe) (gnomAD).

What do computational predictors say about CD163 p.Asp129Gly (c.386A>G)?

AlphaMissense predicts likely benign (score 0.2382) — an in-silico prediction, not a clinical call.

CD163 p.Asp129Gly

c.386A>G · rs149279227 · VCV2378513

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2382 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0103%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2382	likely benign
REVEL	0.218	benign-leaning
SaProt	LLR -9.76	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 6.1	GERP 1.9, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 24 kb · p 1.4e-17 · regional, not allelic
Overall
CADD	24.6	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

Grpmax group 0.0103% European (non-Finnish) · 121/1,180,044 alleles

Filtering AF 0.00876% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0082%

Overall 0.00787% 127/1,614,090 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0103%	9,752
Remaining individualsnot grpmax-eligible	0.0064%	15,623
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606
Admixed American	0.00167%	59,998

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: CD163
Protein: p.Asp129Gly
Coding: c.386A>G
MANE Select: NM_203416
dbSNP: rs149279227
Type: single nucleotide variant
Location: chr12:7501210 (GRCh38)
Gene constraint: LOEUF 0.56 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.72 · 14 PDB
Residue 129: a disulfide bond; the srcr 1 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-asp129gly (accessed [today's date]).

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