Is CD4 p.Lys191Glu (c.571A>G) pathogenic?

CD4 p.Lys191Glu (c.571A>G) is classified Benign in CD4 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-05-29). AlphaMissense: likely benign (0.0652); Low-frequency (popmax 2.08%, afr).

How common is CD4 p.Lys191Glu (c.571A>G) in the general population?

CD4 p.Lys191Glu (c.571A>G) is low-frequency (popmax 2.08%, afr) (gnomAD).

What do computational predictors say about CD4 p.Lys191Glu (c.571A>G)?

AlphaMissense predicts likely benign (score 0.0652) — an in-silico prediction, not a clinical call.

CD4 p.Lys191Glu

c.571A>G · rs28917504 · VCV714505

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0652 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.08%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0652	likely benign
REVEL	0.022	moderately benign-leaning
SaProt	LLR -4.13	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>T here scores Δ0.33 · evaluated, not missing
Constraint at this position
Conservation	phyloP -1.1	GERP -3.9
Regional constraint	o/e 0.83	unconstrained · MANE · 19 kb · p 7.9e-05 · regional, not allelic
Overall
CADD	0.181	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 2.08% African / African-American · 1,559/74,984 alleles

Filtering AF 1.99% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.96%

Overall 0.117% 1,881/1,613,414 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.08%	48
Admixed American	0.198%	504
Remaining individualsnot grpmax-eligible	0.154%	651
Middle Eastern	0.0993%	1,007
European (non-Finnish)	0.00839%	11,915
South Asian	0.0022%	45,522

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.Lys191Glu
Coding: c.571A>G
MANE Select: NM_000616
dbSNP: rs28917504
Type: single nucleotide variant
Location: chr12:6814956 (GRCh38)
Gene constraint: LOEUF 0.673 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.35 · 84 PDB
Residue 191: a UniProt-annotated variant site (in); a β-strand; the ig-like c2-type 1 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-lys191glu (accessed [today's date]).

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