Is MADD p.Arg795Ter (c.2383C>T) pathogenic?

MADD p.Arg795Ter (c.2383C>T) is classified Likely pathogenic in MADD (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-05). Very rare (popmax 0.00134%, afr); Associated with deeah syndrome.

What condition is associated with MADD p.Arg795Ter (c.2383C>T)?

MADD p.Arg795Ter (c.2383C>T) is associated with deeah syndrome (ClinVar).

How common is MADD p.Arg795Ter (c.2383C>T) in the general population?

MADD p.Arg795Ter (c.2383C>T) is very rare (popmax 0.00134%, afr) (gnomAD).

MADD p.Arg795Ter

Q: How is MADD-related developmental delay-endocrine dysfunction-hypohemoglobinemia syndrome inherited?

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

c.2383C>T · rs1327470716 · VCV1334389

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Conditions

deeah syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 13 of 37
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP 1.5, phastCons 1
Overall
CADD	37.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,886 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.00062% 10/1,613,870 alleles · very rare exomes 9/1,461,790 · genomes 1/152,080 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,486
African / African-Americangrpmax	0.00134%	74,886
European (non-Finnish)	0.000678%	147,503

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: MADD
Protein: p.Arg795Ter
Coding: c.2383C>T
MANE Select: NM_001376571
dbSNP: rs1327470716
Type: single nucleotide variant
Location: chr11:47285166 (GRCh38)
Gene constraint: LOEUF 0.725 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.59
Residue 795: a UniProt-annotated variant site (in deeah; uncertain significance); a UniProt-annotated variant site (in deeah and neddish; uncertain significance); the 'disordered' region

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

Disease context

deeah syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For MADD-related developmental delay-endocrine dysfunction-hypohemoglobinemia syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy

Similar variants

MADD c.2816+1G>A Pathogenic ★★ same condition
MADD p.Ala1029Val Uncertain significance ★★ ⚠ same condition
MADD p.Arg754Cys Uncertain significance ★★ ⚠ same condition
MADD p.Cys648Phe Uncertain significance ★★ ⚠ same condition
MADD p.Ile1159Met Uncertain significance ★★ ⚠ same condition
MADD p.Pro372Leu Uncertain significance ★★ ⚠ same condition
MADD p.Val1129Glu Uncertain significance ★★ ⚠ same condition
MADD p.Arg765Gln 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/madd-p-arg795ter (accessed [today's date]).

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