Is FADD p.Asp111= (c.333T>C) pathogenic?

FADD p.Asp111= (c.333T>C) is classified Likely benign in FADD (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-24). Very rare (popmax 0.00329%, sas); Associated with FADD-related immunodeficiency.

What condition is associated with FADD p.Asp111= (c.333T>C)?

FADD p.Asp111= (c.333T>C) is associated with FADD-related immunodeficiency (ClinVar).

How common is FADD p.Asp111= (c.333T>C) in the general population?

FADD p.Asp111= (c.333T>C) is very rare (popmax 0.00329%, sas) (gnomAD).

How is FADD-related immunodeficiency inherited?

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

FADD p.Asp111=

c.333T>C · rs767584770 · VCV1992034

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

Conditions

FADD-related immunodeficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.5	GERP -2.9, phastCons 0.046
Overall
CADD	3.682	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00329% South Asian · 3/91,070 alleles

Filtering AF 0.00114% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000971%

Overall 0.00173% 28/1,614,050 alleles · very rare exomes 26/1,461,862 · genomes 2/152,188 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00329%	30,357
Remaining individualsnot grpmax-eligible	0.0032%	31,250
East Asian	0.00223%	44,874
European (non-Finnish)	0.00178%	56,191
African / African-American	0.00133%	74,998

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.Asp111=
Coding: c.333T>C
MANE Select: NM_003824
dbSNP: rs767584770
Type: single nucleotide variant
Location: chr11:70206179 (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 111: the death domain; a β-strand

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-asp111 (accessed [today's date]).

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