Is CD3E p.Val183Phe (c.547G>T) pathogenic?

CD3E p.Val183Phe (c.547G>T) is classified Uncertain significance in CD3E (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-04). AlphaMissense: likely pathogenic (0.7063); Ultra-rare (popmax 0.0117%, amr); Associated with Inborn genetic diseases.

What condition is associated with CD3E p.Val183Phe (c.547G>T)?

CD3E p.Val183Phe (c.547G>T) is associated with Inborn genetic diseases (ClinVar).

How common is CD3E p.Val183Phe (c.547G>T) in the general population?

CD3E p.Val183Phe (c.547G>T) is ultra-rare (popmax 0.0117%, amr) (gnomAD).

What do computational predictors say about CD3E p.Val183Phe (c.547G>T)?

AlphaMissense predicts likely pathogenic (score 0.7063) — an in-silico prediction, not a clinical call.

CD3E p.Val183Phe

c.547G>T · VCV3488086

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7063 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0117%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7063	likely pathogenic
REVEL	0.264	benign-leaning
SaProt	LLR -9.02	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 1.7, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 11 kb · p 0.052 · regional, not allelic
Overall
CADD	27.5	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 0.0117% Admixed American · 7/59,994 alleles

Filtering AF 0.00543% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0038%

Overall 0.000434% 7/1,613,934 alleles · ultra-rare

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: CD3E
Protein: p.Val183Phe
Coding: c.547G>T
MANE Select: NM_000733
Type: single nucleotide variant
Location: chr11:118314474 (GRCh38)
Gene constraint: LOEUF 0.659 · pLI 0.47 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 73.56 · 44 PDB
Residue 183: an α-helix; the itam domain; the 'disordered' region; the 'numb-binding region' region; the 'proline-rich sequence' region

Full CD3E gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CD3E p.Val183Ala Uncertain significance ★ ⚠ same residue
CD3E p.Arg192Gln Uncertain significance ★★ ⚠ same condition
CD3E p.Cys98Arg Uncertain significance ★★ ⚠ same condition
CD3E p.Ile133Thr Uncertain significance ★★ ⚠ same condition
CD3E p.Tyr150His Uncertain significance ★★ ⚠ same condition
CD3E p.Asn62Ile Uncertain significance ★ ⚠ same condition
CD3E p.Cys49Ser Uncertain significance ★ ⚠ same condition
CD3E p.Glu79Lys Uncertain significance ★ ⚠ same condition

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/cd3e-p-val183phe (accessed [today's date]).

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