Is CD4 p.Val186Ala (c.557T>C) pathogenic?

CD4 p.Val186Ala (c.557T>C) is classified Uncertain significance in CD4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-18). AlphaMissense: ambiguous (0.5522); Absent from gnomAD v4.1.

How common is CD4 p.Val186Ala (c.557T>C) in the general population?

CD4 p.Val186Ala (c.557T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CD4 p.Val186Ala (c.557T>C)?

AlphaMissense predicts ambiguous (score 0.5522) — an in-silico prediction, not a clinical call.

CD4 p.Val186Ala

c.557T>C · rs2542272271 · VCV2476258

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5522 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5522	ambiguous
REVEL	0.077	moderately benign-leaning
SaProt	LLR -8.30	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	Δ0.40	acceptor loss, 8 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 4.7	GERP 2, phastCons 0.86
Regional constraint	o/e 0.83	unconstrained · MANE · 19 kb · p 7.9e-05 · regional, not allelic
Overall
CADD	19.51	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CD4
Protein: p.Val186Ala
Coding: c.557T>C
MANE Select: NM_000616
dbSNP: rs2542272271
Type: single nucleotide variant
Location: chr12:6814942 (GRCh38)
Gene constraint: LOEUF 0.673 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.35 · 84 PDB
Residue 186: 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-val186ala (accessed [today's date]).

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