Is CD4 p.Gln395Lys (c.1183C>A) pathogenic?

CD4 p.Gln395Lys (c.1183C>A) is classified Uncertain significance in CD4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-24). AlphaMissense: likely benign (0.1076); Absent from gnomAD v4.1.

How common is CD4 p.Gln395Lys (c.1183C>A) in the general population?

CD4 p.Gln395Lys (c.1183C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CD4 p.Gln395Lys (c.1183C>A)?

AlphaMissense predicts likely benign (score 0.1076) — an in-silico prediction, not a clinical call.

CD4 p.Gln395Lys

c.1183C>A · rs2542289591 · VCV2529787

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1076 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,612,776)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1076	likely benign
REVEL	0.032	moderately benign-leaning
SaProt	LLR -6.24	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 0.77	GERP -2
Regional constraint	o/e 0.83	unconstrained · MANE · 19 kb · p 7.9e-05 · regional, not allelic
Overall
CADD	9.635	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 1,612,776). 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: CD4
Protein: p.Gln395Lys
Coding: c.1183C>A
MANE Select: NM_000616
dbSNP: rs2542289591
Type: single nucleotide variant
Location: chr12:6818447 (GRCh38)
Gene constraint: LOEUF 0.673 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.35 · 84 PDB

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-gln395lys (accessed [today's date]).

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