Is CD81 p.Leu49Met (c.145C>A) pathogenic?

CD81 p.Leu49Met (c.145C>A) is classified Uncertain significance in CD81 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-26). AlphaMissense: likely benign (0.1902); Absent from gnomAD v4.1.

How common is CD81 p.Leu49Met (c.145C>A) in the general population?

CD81 p.Leu49Met (c.145C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CD81 p.Leu49Met (c.145C>A)?

AlphaMissense predicts likely benign (score 0.1902) — an in-silico prediction, not a clinical call.

CD81 p.Leu49Met

c.145C>A · rs2496509400 · VCV2826148

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1902 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,612,956)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1902	likely benign
REVEL	0.348	indeterminate
SaProt	LLR -8.75	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.9	GERP -2.1, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 17 kb · p 0.15 · regional, not allelic
Overall
CADD	22.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

No allele count reported in gnomAD v4.1 (AN 1,612,956). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CD81
Protein: p.Leu49Met
Coding: c.145C>A
MANE Select: NM_004356
dbSNP: rs2496509400
Type: single nucleotide variant
Location: chr11:2390490 (GRCh38)
Gene constraint: LOEUF 0.702 · pLI 0.36 (gnomAD)
Structure: AlphaFold pLDDT 87.24 · 16 PDB

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-leu49met (accessed [today's date]).

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