Is CD68 p.Phe218Leu (c.652T>C) pathogenic?

CD68 p.Phe218Leu (c.652T>C) is classified Uncertain significance in CD68 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-11). AlphaMissense: likely pathogenic (0.9772); Absent from gnomAD v4.1.

How common is CD68 p.Phe218Leu (c.652T>C) in the general population?

CD68 p.Phe218Leu (c.652T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CD68 p.Phe218Leu (c.652T>C)?

AlphaMissense predicts likely pathogenic (score 0.9772) — an in-silico prediction, not a clinical call.

CD68 p.Phe218Leu

c.652T>C · rs2508502781 · VCV2232677

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9772 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9772	likely pathogenic · top 1% in CD68
REVEL	0.375	indeterminate
SaProt	LLR -8.71	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.4, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 1,830 bp · p 0.38 · regional, not allelic
Overall
CADD	26.9	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: CD68
Protein: p.Phe218Leu
Coding: c.652T>C
MANE Select: NM_001251
dbSNP: rs2508502781
Type: single nucleotide variant
Location: chr17:7580550 (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-phe218leu (accessed [today's date]).

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