Is FADD p.Ala86= (c.258G>A) pathogenic?

FADD p.Ala86= (c.258G>A) is classified Likely benign in FADD (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-18). Very rare (popmax 0.00321%, amr); Associated with FADD-related immunodeficiency.

What condition is associated with FADD p.Ala86= (c.258G>A)?

FADD p.Ala86= (c.258G>A) is associated with FADD-related immunodeficiency (ClinVar).

How common is FADD p.Ala86= (c.258G>A) in the general population?

FADD p.Ala86= (c.258G>A) is very rare (popmax 0.00321%, amr) (gnomAD).

How is FADD-related immunodeficiency inherited?

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

FADD p.Ala86=

c.258G>A · rs2049439639 · VCV1582435

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00321%, amr)

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 -0.12	GERP -3.1
Overall
CADD	7.66	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00321% Admixed American · 1/31,154 alleles

Overall 7.06e-05% 1/1,416,472 alleles · very rare exomes 1/1,264,270 · genomes 0/152,202 · joint denominator

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.Ala86=
Coding: c.258G>A
MANE Select: NM_003824
dbSNP: rs2049439639
Type: single nucleotide variant
Location: chr11:70203717 (GRCh38)
Gene constraint: LOEUF 1.715 · pLI 0.07 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 72.60 · 18 PDB

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-ala86 (accessed [today's date]).

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