Is ARAP1 p.Thr699Met (c.2096C>T) pathogenic?

ARAP1 p.Thr699Met (c.2096C>T) is classified Uncertain significance in ARAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-24). AlphaMissense: likely benign (0.1737); Rare (popmax 0.141%, sas).

How common is ARAP1 p.Thr699Met (c.2096C>T) in the general population?

ARAP1 p.Thr699Met (c.2096C>T) is rare (popmax 0.141%, sas) (gnomAD).

What do computational predictors say about ARAP1 p.Thr699Met (c.2096C>T)?

AlphaMissense predicts likely benign (score 0.1737) — an in-silico prediction, not a clinical call.

ARAP1 p.Thr699Met

c.2096C>T · VCV3309406

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1737 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.141%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1737	likely benign
REVEL	0.171	moderately benign-leaning
SaProt	LLR -14.09	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.7, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 15 kb · p 7.9e-09 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.141% South Asian · 120/85,212 alleles

Filtering AF 0.12% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.113%

Overall 0.0564% 885/1,568,130 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.141%	710
European (non-Finnish)	0.0613%	1,633
Remaining individualsnot grpmax-eligible	0.0362%	2,765
Middle Eastern	0.0333%	3,001
Finnishnot grpmax-eligible	0.025%	4,003
Admixed American	0.0172%	5,823
African / African-American	0.00947%	10,562
Ashkenazi Jewishnot grpmax-eligible	0.00347%	28,834

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: ARAP1
Protein: p.Thr699Met
Coding: c.2096C>T
MANE Select: NM_001040118
Type: single nucleotide variant
Location: chr11:72702976 (GRCh38)
Gene constraint: LOEUF 0.572 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.81 · 1 PDB

Full ARAP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ARAP1 p.Gln1047Glu Benign ★★ same type
ARAP1 p.Pro1039= Benign ★★ same type
ARAP1 p.Pro254Leu Benign ★★ same type
ARAP1 p.Val1408Met Benign ★★ ⚠ same type
ARAP1 p.Ala1046Ser Uncertain significance ★ ⚠ same type
ARAP1 p.Ala1124Thr Uncertain significance ★ ⚠ same type
ARAP1 p.Ala1199Thr Uncertain significance ★ ⚠ same type
ARAP1 p.Ala1389Thr 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/arap1-p-thr699met (accessed [today's date]).

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