Is ASAP3 p.Leu147= (c.441G>C) pathogenic?

ASAP3 p.Leu147= (c.441G>C) is classified Benign in ASAP3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-03-02). Common (popmax 8.03%, afr) — too common for a highly-penetrant pathogenic allele.

ASAP3 p.Leu147=

Q: How common is ASAP3 p.Leu147= (c.441G>C) in the general population?

ASAP3 p.Leu147= (c.441G>C) is common (popmax 8.03%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.441G>C · rs74062718 · VCV784938

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 8.03%, afr) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>T here scores Δ0.26 · evaluated, not missing
Constraint at this position
Conservation	phyloP 4.7	GERP 0.89, phastCons 1
Overall
CADD	12.18	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.03% African / African-American · 6,019/74,994 alleles

Filtering AF 7.86% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.79%

Overall 0.41% 6,620/1,614,142 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	8.03%	12
Remaining individualsnot grpmax-eligible	0.418%	239
Admixed American	0.357%	280
Middle Eastern	0.165%	606
South Asian	0.0209%	4,794
European (non-Finnish)	0.00822%	12,165

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.Leu147=
Coding: c.441G>C
MANE Select: NM_017707
dbSNP: rs74062718
Type: single nucleotide variant
Location: chr1:23451511 (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.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
ASAP3 p.Ala619Ser 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-leu147 (accessed [today's date]).

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