Is FADD p.Ala207Val (c.620C>T) pathogenic?

FADD p.Ala207Val (c.620C>T) is classified Conflicting classifications of pathogenicity in FADD (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-01-21). AlphaMissense: likely benign (0.1081); Rare (popmax 0.33%, afr); Associated with FADD-related immunodeficiency.

What condition is associated with FADD p.Ala207Val (c.620C>T)?

FADD p.Ala207Val (c.620C>T) is associated with FADD-related immunodeficiency (ClinVar).

How common is FADD p.Ala207Val (c.620C>T) in the general population?

FADD p.Ala207Val (c.620C>T) is rare (popmax 0.33%, afr) (gnomAD).

How is FADD-related immunodeficiency inherited?

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

What do computational predictors say about FADD p.Ala207Val (c.620C>T)?

AlphaMissense predicts likely benign (score 0.1081) — an in-silico prediction, not a clinical call.

FADD p.Ala207Val

c.620C>T · rs146934620 · VCV1128791

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1081 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.33%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

FADD-related immunodeficiency

Computational evidence

Protein change
AlphaMissense	0.1081	likely benign
REVEL	0.161	moderately benign-leaning
SaProt	LLR -5.81	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.071	GERP -2.9
Regional constraint	o/e 0.87	unconstrained · MANE · 3,010 bp · p 0.026 · regional, not allelic
Overall
CADD	6.806	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 0.33% African / African-American · 248/75,052 alleles

Filtering AF 0.297% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.283%

Overall 0.0174% 280/1,613,686 alleles · rare exomes 129/1,461,388 · genomes 151/152,298 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.33%	303
Remaining individualsnot grpmax-eligible	0.0192%	5,208
Middle Eastern	0.0165%	6,058
Admixed American	0.00833%	12,004
South Asian	0.00329%	30,359
European (non-Finnish)	0.000932%	107,268

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.Ala207Val
Coding: c.620C>T
MANE Select: NM_003824
dbSNP: rs146934620
Type: single nucleotide variant
Location: chr11:70206466 (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 207: the 'disordered' region

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.Ala207= Likely benign ★ same residue
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

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-ala207val (accessed [today's date]).

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