Is ADAP1 p.Thr267Arg (c.800C>G) pathogenic?

ADAP1 p.Thr267Arg (c.800C>G) is classified Uncertain significance in ADAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-05). AlphaMissense: likely benign (0.2237); Ultra-rare (popmax 0.0107%, nfe).

How common is ADAP1 p.Thr267Arg (c.800C>G) in the general population?

ADAP1 p.Thr267Arg (c.800C>G) is ultra-rare (popmax 0.0107%, nfe) (gnomAD).

What do computational predictors say about ADAP1 p.Thr267Arg (c.800C>G)?

AlphaMissense predicts likely benign (score 0.2237) — an in-silico prediction, not a clinical call.

ADAP1 p.Thr267Arg

c.800C>G · VCV3493221

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2237 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0107%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2237	likely benign
REVEL	0.236	benign-leaning
SaProt	LLR -8.41	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.5	GERP 4.4, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 56 kb · p 0.32 · regional, not allelic
Overall
CADD	23.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0107% European (non-Finnish) · 126/1,179,796 alleles

Filtering AF 0.00911% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00855%

Overall 0.00794% 128/1,612,656 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0107%	9,363
African / African-American	0.00267%	37,456

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.Thr267Arg
Coding: c.800C>G
MANE Select: NM_006869
Type: single nucleotide variant
Location: chr7:899486 (GRCh38)
Gene constraint: LOEUF 0.949 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.96 · 4 PDB
Residue 267: the ph 2 domain

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-thr267arg (accessed [today's date]).

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