Is CD81 p.Leu78= (c.232C>T) pathogenic?

CD81 p.Leu78= (c.232C>T) is classified Likely benign in CD81 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-09). Very rare (popmax 0.00223%, eas).

How common is CD81 p.Leu78= (c.232C>T) in the general population?

CD81 p.Leu78= (c.232C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

CD81 p.Leu78=

c.232C>T · rs2496527450 · VCV2712988

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.6	GERP -0.23, phastCons 1
Overall
CADD	11.12	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,848 alleles

Overall 0.000137% 2/1,461,088 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,848
Remaining individualsnot grpmax-eligible	0.0016%	62,496

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: CD81
Protein: p.Leu78=
Coding: c.232C>T
MANE Select: NM_004356
dbSNP: rs2496527450
Type: single nucleotide variant
Location: chr11:2394145 (GRCh38)
Gene constraint: LOEUF 0.702 · pLI 0.36 (gnomAD)
Structure: AlphaFold pLDDT 87.24 · 16 PDB
Residue 78: an α-helix

Full CD81 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CD81 c.561+5G>A Uncertain significance ★★ same type
CD81 p.Ala120Thr Uncertain significance ★★ ⚠ same type
CD81 p.Ala54Val Uncertain significance ★★ same type
CD81 p.Arg231Gln Uncertain significance ★★ ⚠ same type
CD81 p.Asn115Ser Uncertain significance ★★ ⚠ same type
CD81 p.Asn141Lys Uncertain significance ★★ ⚠ same type
CD81 p.Asn141Ser Uncertain significance ★★ ⚠ same type
CD81 p.Asn173Asp 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/cd81-p-leu78 (accessed [today's date]).

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