Is CD68 p.Arg346Gly (c.1036A>G) pathogenic?

CD68 p.Arg346Gly (c.1036A>G) is classified Uncertain significance in CD68 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-01). AlphaMissense: likely benign (0.1515); Very rare (popmax 0.00401%, afr).

How common is CD68 p.Arg346Gly (c.1036A>G) in the general population?

CD68 p.Arg346Gly (c.1036A>G) is very rare (popmax 0.00401%, afr) (gnomAD).

What do computational predictors say about CD68 p.Arg346Gly (c.1036A>G)?

AlphaMissense predicts likely benign (score 0.1515) — an in-silico prediction, not a clinical call.

CD68 p.Arg346Gly

c.1036A>G · rs781304672 · VCV2480230

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1515 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00401%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1515	likely benign
REVEL	0.434	indeterminate
SaProt	LLR -10.44	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP 0.15, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 1,830 bp · p 0.38 · regional, not allelic
Overall
CADD	24.1	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

Grpmax group 0.00401% African / African-American · 3/74,854 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000991% 16/1,613,954 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00401%	24,951
South Asian	0.0011%	91,084
European (non-Finnish)	0.00102%	98,336

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: CD68
Protein: p.Arg346Gly
Coding: c.1036A>G
MANE Select: NM_001251
dbSNP: rs781304672
Type: single nucleotide variant
Location: chr17:7581482 (GRCh38)
Gene constraint: LOEUF 1.013 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.23

Full CD68 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CD68 p.Ile329Thr Benign ★★ same type
CD68 p.Ala10Val Uncertain significance ★ ⚠ same type
CD68 p.Ala262Thr Uncertain significance ★ ⚠ same type
CD68 p.Ala269Val Uncertain significance ★ ⚠ same type
CD68 p.Ala299Asp Uncertain significance ★ ⚠ same type
CD68 p.Ala99Thr Uncertain significance ★ ⚠ same type
CD68 p.Arg345Pro Uncertain significance ★ ⚠ same type
CD68 p.Arg345Trp 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/cd68-p-arg346gly (accessed [today's date]).

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