Is FADD p.Phe4= (c.12C>T) pathogenic?

FADD p.Phe4= (c.12C>T) is classified Likely benign in FADD (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-26). Very rare (popmax 0.00464%, eas); Associated with FADD-related immunodeficiency.

What condition is associated with FADD p.Phe4= (c.12C>T)?

FADD p.Phe4= (c.12C>T) is associated with FADD-related immunodeficiency (ClinVar).

How common is FADD p.Phe4= (c.12C>T) in the general population?

FADD p.Phe4= (c.12C>T) is very rare (popmax 0.00464%, eas) (gnomAD).

How is FADD-related immunodeficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

FADD p.Phe4=

c.12C>T · VCV3716151

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00464%, eas)

Conditions

FADD-related immunodeficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.3	GERP 0.54, phastCons 0.99
Overall
CADD	11.87	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00464% East Asian · 2/43,140 alleles

Filtering AF 0.000768% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000287%

Overall 0.000316% 5/1,584,324 alleles · very rare exomes 5/1,432,310 · genomes 0/152,014 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00464%	21,570
African / African-American	0.00135%	74,258
European (non-Finnish)	0.000172%	582,795

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: FADD
Protein: p.Phe4=
Coding: c.12C>T
MANE Select: NM_003824
Type: single nucleotide variant
Location: chr11:70203471 (GRCh38)
Gene constraint: LOEUF 1.715 · pLI 0.07 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 72.60 · 18 PDB
Residue 4: the ded domain; an α-helix

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

Disease context

FADD-related immunodeficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For FADD-related immunodeficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

FADD p.Ala156Thr Uncertain significance ★★ same condition
FADD p.Asp106Asn Uncertain significance ★★ ⚠ same condition
FADD p.Ile126Met Uncertain significance ★★ ⚠ same condition
FADD p.Met193Thr Uncertain significance ★★ ⚠ same condition
FADD p.Ser18Arg Uncertain significance ★★ ⚠ same condition
FADD p.Thr151Ile Uncertain significance ★★ ⚠ same condition
FADD p.Val103Ile Uncertain significance ★★ ⚠ same condition
FADD c.286+20G>A Likely benign ★★ 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/fadd-p-phe4 (accessed [today's date]).

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