Is CD86 p.Asp104Glu (c.312C>G) pathogenic?

CD86 p.Asp104Glu (c.312C>G) is classified Uncertain significance in CD86 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-11). AlphaMissense: likely pathogenic (0.8986); Very rare (popmax 8.48e-05%, nfe).

How common is CD86 p.Asp104Glu (c.312C>G) in the general population?

CD86 p.Asp104Glu (c.312C>G) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about CD86 p.Asp104Glu (c.312C>G)?

AlphaMissense predicts likely pathogenic (score 0.8986) — an in-silico prediction, not a clinical call.

CD86 p.Asp104Glu

c.312C>G · VCV4223067

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8986 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8986	likely pathogenic · top 6% in CD86
REVEL	0.827	moderately pathogenic-leaning
SaProt	LLR -11.13	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.084	GERP -0.94, phastCons 0.004
Regional constraint	o/e 0.90	unconstrained · MANE · 64 kb · p 0.048 · regional, not allelic
Overall
CADD	21.9	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

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,898 alleles

Overall 6.84e-05% 1/1,461,734 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: CD86
Protein: p.Asp104Glu
Coding: c.312C>G
MANE Select: NM_175862
Type: single nucleotide variant
Location: chr3:122103759 (GRCh38)
Gene constraint: LOEUF 0.555 · pLI 0.93 (gnomAD)
Structure: AlphaFold pLDDT 80.10 · 7 PDB
Residue 104: a disulfide bond; an α-helix; the ig-like v-type domain

Full CD86 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CD86 p.Ala310Thr Benign ★★ same type
CD86 p.Asp323Asn Benign ★★ same type
CD86 p.Ala24Val Uncertain significance ★ ⚠ same type
CD86 p.Arg277Cys Uncertain significance ★ ⚠ same type
CD86 p.Arg277His Uncertain significance ★ ⚠ same type
CD86 p.Arg306Ile Uncertain significance ★ ⚠ same type
CD86 p.Gln311Glu Uncertain significance ★ ⚠ same type
CD86 p.Glu181Ala 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/cd86-p-asp104glu (accessed [today's date]).

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