Is ASAP3 p.Leu268Phe (c.802C>T) pathogenic?

ASAP3 p.Leu268Phe (c.802C>T) is classified Uncertain significance in ASAP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-11). AlphaMissense: ambiguous (0.3499); Very rare (popmax 0.00133%, afr).

How common is ASAP3 p.Leu268Phe (c.802C>T) in the general population?

ASAP3 p.Leu268Phe (c.802C>T) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about ASAP3 p.Leu268Phe (c.802C>T)?

AlphaMissense predicts ambiguous (score 0.3499) — an in-silico prediction, not a clinical call.

ASAP3 p.Leu268Phe

c.802C>T · VCV3433851

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3499 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Computational evidence

Protein change
AlphaMissense	0.3499	ambiguous
REVEL	0.345	indeterminate
SaProt	LLR -9.46	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.1, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 54 kb · p 1.4e-05 · regional, not allelic
Overall
CADD	25.5	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 0.00133% African / African-American · 1/75,070 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000479% 7/1,461,802 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	75,070
European (non-Finnish)	0.000508%	196,672

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: ASAP3
Protein: p.Leu268Phe
Coding: c.802C>T
MANE Select: NM_017707
Type: single nucleotide variant
Location: chr1:23441419 (GRCh38)
Gene constraint: LOEUF 0.864 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.62 · 4 PDB

Full ASAP3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ASAP3 p.Asp314= Benign ★★ same type
ASAP3 p.Glu377Ala Benign ★★ ⚠ same type
ASAP3 p.Leu147= Benign ★★ same type
ASAP3 p.Ala103Thr Uncertain significance ★ ⚠ same type
ASAP3 p.Ala221Thr Uncertain significance ★ ⚠ same type
ASAP3 p.Ala244Val Uncertain significance ★ ⚠ same type
ASAP3 p.Ala415Val Uncertain significance ★ ⚠ same type
ASAP3 p.Ala566Thr 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/asap3-p-leu268phe (accessed [today's date]).

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