Is ASAP1 p.Phe873Leu (c.2619T>G) pathogenic?

ASAP1 p.Phe873Leu (c.2619T>G) is classified Uncertain significance in ASAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-06). AlphaMissense: likely pathogenic (0.8789); Very rare (popmax 0.00178%, nfe).

How common is ASAP1 p.Phe873Leu (c.2619T>G) in the general population?

ASAP1 p.Phe873Leu (c.2619T>G) is very rare (popmax 0.00178%, nfe) (gnomAD).

What do computational predictors say about ASAP1 p.Phe873Leu (c.2619T>G)?

AlphaMissense predicts likely pathogenic (score 0.8789) — an in-silico prediction, not a clinical call.

ASAP1 p.Phe873Leu

c.2619T>G · rs1383437544 · VCV2474249

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8789 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00178%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8789	likely pathogenic
REVEL	0.137	moderately benign-leaning
SaProt	LLR -4.15	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.54	GERP -3.2, phastCons 0.84
Regional constraint	o/e 0.94	unconstrained · MANE · 39 kb · p 0.25 · regional, not allelic
Overall
CADD	16.18	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 0.00178% European (non-Finnish) · 21/1,180,024 alleles

Filtering AF 0.00114% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000971%

Overall 0.00142% 23/1,614,076 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00178%	56,192
Remaining individualsnot grpmax-eligible	0.0016%	62,484
African / African-American	0.00133%	74,934

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.Phe873Leu
Coding: c.2619T>G
MANE Select: NM_018482
dbSNP: rs1383437544
Type: single nucleotide variant
Location: chr8:130079925 (GRCh38)
Gene constraint: LOEUF 0.439 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.05 · 5 PDB
Residue 873: 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-phe873leu (accessed [today's date]).

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