Is ASAP1 p.Thr1054= (c.3162G>A) pathogenic?

ASAP1 p.Thr1054= (c.3162G>A) is classified Likely benign in ASAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-01). Rare (popmax 0.282%, sas).

How common is ASAP1 p.Thr1054= (c.3162G>A) in the general population?

ASAP1 p.Thr1054= (c.3162G>A) is rare (popmax 0.282%, sas) (gnomAD).

ASAP1 p.Thr1054=

c.3162G>A · rs140674458 · VCV2658816

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.282%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.048	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -14	GERP -5
Overall
CADD	0.907	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.282% South Asian · 257/90,978 alleles

Filtering AF 0.264% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.26%

Overall 0.245% 3,949/1,613,584 alleles · rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.647%	155
South Asiangrpmax	0.282%	354
European (non-Finnish)	0.271%	368
Remaining individualsnot grpmax-eligible	0.248%	403
Middle Eastern	0.231%	432
Admixed American	0.152%	659
African / African-American	0.0427%	2,345
Finnishnot grpmax-eligible	0.0109%	9,143

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: ASAP1
Protein: p.Thr1054=
Coding: c.3162G>A
MANE Select: NM_018482
dbSNP: rs140674458
Type: single nucleotide variant
Location: chr8:130060609 (GRCh38)
Gene constraint: LOEUF 0.439 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.05 · 5 PDB
Residue 1054: the 'disordered' region

Full ASAP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ASAP1 p.Gln263= Benign ★★ same type
ASAP1 p.Ala1035Gly Uncertain significance ★ ⚠ same type
ASAP1 p.Ala429Val Uncertain significance ★ ⚠ same type
ASAP1 p.Ala914Gly Uncertain significance ★ ⚠ same type
ASAP1 p.Arg212His Uncertain significance ★ ⚠ same type
ASAP1 p.Arg447Gln Uncertain significance ★ ⚠ same type
ASAP1 p.Arg710Ter Uncertain significance ★ same type
ASAP1 p.Arg764Gln 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/asap1-p-thr1054 (accessed [today's date]).

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