Is ADD3 p.Ter707= (c.2119TAAA[1]) pathogenic?

ADD3 p.Ter707= (c.2119TAAA[1]) is classified Conflicting classifications of pathogenicity in ADD3 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-12-28). Rare (popmax 0.495%, mid).

How common is ADD3 p.Ter707= (c.2119TAAA[1]) in the general population?

ADD3 p.Ter707= (c.2119TAAA[1]) is rare (popmax 0.495%, mid) (gnomAD).

ADD3 p.Ter707=

c.2119TAAA[1] · rs753541585 · VCV445451

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

Consequence

stop-loss

predicted LoF

gnomAD v4.1

Rare

rare (popmax 0.495%, mid)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	stop-loss	predicted loss-of-function in a LoF-intolerant gene
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.4	GERP 0.46, phastCons 1
Overall
CADD	6.471	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 0.495% Middle Eastern · 29/5,860 alleles

Filtering AF 0.354% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.306%

Overall 0.0251% 394/1,570,816 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.495%	202
Ashkenazi Jewishnot grpmax-eligible	0.404%	248
Remaining individualsnot grpmax-eligible	0.0676%	1,478
European (non-Finnish)	0.0162%	6,163
Admixed American	0.0138%	7,235
African / African-American	0.00965%	10,364
South Asian	0.00954%	10,483
East Asian	0.00225%	44,534

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: ADD3
Protein: p.Ter707=
Coding: c.2119TAAA[1]
MANE Select: NM_016824
dbSNP: rs753541585
Type: Microsatellite
Location: chr10:110133616 (GRCh38)
Gene constraint: LOEUF 0.395 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 66.83

Full ADD3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ADD3 c.1521+15_1521+17del Benign ★ 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/add3-p-ter707 (accessed [today's date]).

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