Is CD4 p.Arg265Trp (c.793C>T) pathogenic?

CD4 p.Arg265Trp (c.793C>T) is classified Benign in CD4 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2020-10-28). AlphaMissense: likely benign (0.0903); Common (popmax 19.9%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Okt4 epitope deficiency.

What condition is associated with CD4 p.Arg265Trp (c.793C>T)?

CD4 p.Arg265Trp (c.793C>T) is associated with Okt4 epitope deficiency (ClinVar).

What do computational predictors say about CD4 p.Arg265Trp (c.793C>T)?

AlphaMissense predicts likely benign (score 0.0903) — an in-silico prediction, not a clinical call.

CD4 p.Arg265Trp

Q: How common is CD4 p.Arg265Trp (c.793C>T) in the general population?

CD4 p.Arg265Trp (c.793C>T) is common (popmax 19.9%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.793C>T · rs28919570 · VCV29898

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.0903 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 19.9%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Okt4 epitope deficiency

Computational evidence

Protein change
AlphaMissense	0.0903	likely benign
REVEL	0.036	moderately benign-leaning
SaProt	LLR -9.67	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 -1.6	GERP -3
Regional constraint	o/e 0.83	unconstrained · MANE · 19 kb · p 7.9e-05 · regional, not allelic
Overall
CADD	0.464	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 19.9% African / African-American · 14,953/74,972 alleles

Filtering AF 19.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 19.6%

Overall 1.33% 21,521/1,614,120 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	19.9%	5
East Asian	4.61%	22
Remaining individualsnot grpmax-eligible	1.75%	57
Admixed American	1.74%	57
Ashkenazi Jewishnot grpmax-eligible	1.6%	62
Middle Eastern	1.4%	71
South Asian	0.458%	218
European (non-Finnish)	0.117%	854

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.Arg265Trp
Coding: c.793C>T
MANE Select: NM_000616
dbSNP: rs28919570
Type: single nucleotide variant
Location: chr12:6816241 (GRCh38)
Gene constraint: LOEUF 0.673 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.35 · 84 PDB
Residue 265: a UniProt-annotated variant site (in okt4-negative populations); the ig-like c2-type 2 domain

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

Disease context

Okt4 epitope deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CD4 p.Thr444Ala Uncertain significance ★★ ⚠ same condition
CD4 p.Thr267Ala Uncertain significance ★ ⚠ same condition
CD4 p.Ser352Trp 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.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-arg265trp (accessed [today's date]).

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