Is CD68 p.Ser85Arg (c.253A>C) pathogenic?

CD68 p.Ser85Arg (c.253A>C) is classified Uncertain significance in CD68 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-30). AlphaMissense: likely benign (0.2334); Very rare (popmax 0.00102%, nfe).

How common is CD68 p.Ser85Arg (c.253A>C) in the general population?

CD68 p.Ser85Arg (c.253A>C) is very rare (popmax 0.00102%, nfe) (gnomAD).

What do computational predictors say about CD68 p.Ser85Arg (c.253A>C)?

AlphaMissense predicts likely benign (score 0.2334) — an in-silico prediction, not a clinical call.

CD68 p.Ser85Arg

c.253A>C · rs1225189329 · VCV3140648

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2334 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00102%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2334	likely benign
REVEL	0.06	moderately benign-leaning
SaProt	LLR -11.77	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.28	GERP -0.54
Regional constraint	o/e 1.04	unconstrained · MANE · 1,830 bp · p 0.38 · regional, not allelic
Overall
CADD	6.422	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 0.00102% European (non-Finnish) · 12/1,175,910 alleles

Filtering AF 0.000544% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00043%

Overall 0.000746% 12/1,609,000 alleles · very rare

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.Ser85Arg
Coding: c.253A>C
MANE Select: NM_001251
dbSNP: rs1225189329
Type: single nucleotide variant
Location: chr17:7580013 (GRCh38)
Gene constraint: LOEUF 1.013 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.23
Residue 85: the 'mucin-like' region; the 'disordered' region; the '2 x 30 aa tandem repeats' region

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-ser85arg (accessed [today's date]).

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