Is ADAP1 p.Thr307= (c.921G>A) pathogenic?

ADAP1 p.Thr307= (c.921G>A) is classified Benign in ADAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-06-18). Common (popmax 9.27%, afr) — too common for a highly-penetrant pathogenic allele.

ADAP1 p.Thr307=

Q: How common is ADAP1 p.Thr307= (c.921G>A) in the general population?

ADAP1 p.Thr307= (c.921G>A) is common (popmax 9.27%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.921G>A · rs61995731 · VCV776189

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 9.27%, afr) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.055	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.7	GERP -1.3
Overall
CADD	8.791	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 9.27% African / African-American · 6,958/75,034 alleles

Filtering AF 9.09% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.02%

Overall 0.504% 8,121/1,612,652 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	9.27%	11
Remaining individualsnot grpmax-eligible	0.642%	156
Admixed American	0.565%	177
Middle Eastern	0.429%	233
European (non-Finnish)	0.0314%	3,180
South Asian	0.0285%	3,504

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: ADAP1
Protein: p.Thr307=
Coding: c.921G>A
MANE Select: NM_006869
dbSNP: rs61995731
Type: single nucleotide variant
Location: chr7:899208 (GRCh38)
Gene constraint: LOEUF 0.949 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.96 · 4 PDB
Residue 307: the ph 2 domain; a β-strand

Full ADAP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ADAP1 p.Ala168Val Uncertain significance ★ same type
ADAP1 p.Ala182Thr Uncertain significance ★ ⚠ same type
ADAP1 p.Ala243Thr Uncertain significance ★ ⚠ same type
ADAP1 p.Ala26Val Uncertain significance ★ ⚠ same type
ADAP1 p.Ala293Val Uncertain significance ★ ⚠ same type
ADAP1 p.Ala349Val Uncertain significance ★ ⚠ same type
ADAP1 p.Ala81Glu Uncertain significance ★ ⚠ same type
ADAP1 p.Ala81Val 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/adap1-p-thr307 (accessed [today's date]).

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