Is ADD1 p.Pro43= (c.129A>G) pathogenic?

ADD1 p.Pro43= (c.129A>G) is classified Likely benign in ADD1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-03-20). Rare (popmax 0.363%, mid); Associated with ADD1-related disorder.

What condition is associated with ADD1 p.Pro43= (c.129A>G)?

ADD1 p.Pro43= (c.129A>G) is associated with ADD1-related disorder (ClinVar).

How common is ADD1 p.Pro43= (c.129A>G) in the general population?

ADD1 p.Pro43= (c.129A>G) is rare (popmax 0.363%, mid) (gnomAD).

ADD1 p.Pro43=

c.129A>G · rs146519461 · VCV3033151

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.363%, mid)

Conditions

ADD1-related disorder

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 -0.99	GERP -3.5
Overall
CADD	5.431	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.363% Middle Eastern · 22/6,062 alleles

Filtering AF 0.246% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.207%

Overall 0.0573% 925/1,614,168 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.363%	276
Ashkenazi Jewishnot grpmax-eligible	0.24%	417
Admixed American	0.175%	572
Remaining individualsnot grpmax-eligible	0.141%	710
African / African-American	0.0933%	1,072
European (non-Finnish)	0.0481%	2,081
South Asian	0.0022%	45,539

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: ADD1
Protein: p.Pro43=
Coding: c.129A>G
MANE Select: NM_001354761
dbSNP: rs146519461
Type: single nucleotide variant
Location: chr4:2876044 (GRCh38)
Gene constraint: LOEUF 0.387 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 65.73

Full ADD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ADD1-related disorder

Similar variants

ADD1 p.Ala18Thr Uncertain significance ★ ⚠ same condition
ADD1 p.Val234= Benign ★★ same type
ADD1 p.Val559Met Benign ★★ same type
ADD1 c.2047+530G>A Uncertain significance ★ same type
ADD1 c.2047+541G>T Uncertain significance ★ same type
ADD1 p.Ala137Val Uncertain significance ★ ⚠ same type
ADD1 p.Ala151Thr Uncertain significance ★ ⚠ same type
ADD1 p.Ala156Thr Uncertain significance ★ ⚠ same type

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/add1-p-pro43 (accessed [today's date]).

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