Is ASAP3 p.Leu120Phe (c.360G>C) pathogenic?

ASAP3 p.Leu120Phe (c.360G>C) is classified Uncertain significance in ASAP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-24). AlphaMissense: ambiguous (0.4286); Rare (popmax 0.773%, mid).

How common is ASAP3 p.Leu120Phe (c.360G>C) in the general population?

ASAP3 p.Leu120Phe (c.360G>C) is rare (popmax 0.773%, mid) (gnomAD).

What do computational predictors say about ASAP3 p.Leu120Phe (c.360G>C)?

AlphaMissense predicts ambiguous (score 0.4286) — an in-silico prediction, not a clinical call.

ASAP3 p.Leu120Phe

c.360G>C · rs201194561 · VCV2354749

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4286 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.773%, mid)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4286	ambiguous
REVEL	0.203	benign-leaning
SaProt	LLR -8.42	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.50 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.3	GERP 1.1, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 54 kb · p 1.4e-05 · regional, not allelic
Overall
CADD	22.7	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 0.773% Middle Eastern · 47/6,084 alleles

Filtering AF 0.597% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.535%

Overall 0.0141% 228/1,613,806 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.773%	129
Remaining individualsnot grpmax-eligible	0.032%	3,124
African / African-American	0.0134%	7,490
Admixed American	0.0133%	7,501
South Asian	0.0132%	7,590
European (non-Finnish)	0.0111%	9,008

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.Leu120Phe
Coding: c.360G>C
MANE Select: NM_017707
dbSNP: rs201194561
Type: single nucleotide variant
Location: chr1:23452760 (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-leu120phe (accessed [today's date]).

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