Is CD4 p.Leu361Pro (c.1082T>C) pathogenic?

CD4 p.Leu361Pro (c.1082T>C) is classified Uncertain significance in CD4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-23). AlphaMissense: likely benign (0.063); Very rare (popmax 0.000681%, nfe).

How common is CD4 p.Leu361Pro (c.1082T>C) in the general population?

CD4 p.Leu361Pro (c.1082T>C) is very rare (popmax 0.000681%, nfe) (gnomAD).

What do computational predictors say about CD4 p.Leu361Pro (c.1082T>C)?

AlphaMissense predicts likely benign (score 0.063) — an in-silico prediction, not a clinical call.

CD4 p.Leu361Pro

c.1082T>C · rs1555118104 · VCV2605865

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.063 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000681%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.063	likely benign
REVEL	0.051	moderately benign-leaning
SaProt	LLR -5.22	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -11	GERP -3.8
Regional constraint	o/e 0.83	unconstrained · MANE · 19 kb · p 7.9e-05 · regional, not allelic
Overall
CADD	0.027	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

Grpmax group 0.000681% European (non-Finnish) · 8/1,175,256 alleles

Filtering AF 0.000293% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000212%

Overall 0.000498% 8/1,605,092 alleles · very rare exomes 8/1,452,812 · genomes 0/152,280 · joint denominator

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: CD4
Protein: p.Leu361Pro
Coding: c.1082T>C
MANE Select: NM_000616
dbSNP: rs1555118104
Type: single nucleotide variant
Location: chr12:6817256 (GRCh38)
Gene constraint: LOEUF 0.673 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.35 · 84 PDB
Residue 361: the ig-like c2-type 3 domain

Full CD4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CD4 p.Ser352Trp Uncertain significance ★★ ⚠ same type
CD4 p.Thr444Ala Uncertain significance ★★ ⚠ same type
CD4 c.1346+55T>G Benign ★★ same type
CD4 c.49+35A>G Benign ★★ same type
CD4 c.*91C>A Benign ★★ same type
CD4 c.*92A>G Benign ★★ same type
CD4 p.Arg265Trp Benign ★★ same type
CD4 p.Arg431Gln Benign/Likely benign ★★ 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/cd4-p-leu361pro (accessed [today's date]).

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