Is AHSG p.Leu13= (c.39C>G) pathogenic?

AHSG p.Leu13= (c.39C>G) is classified Benign in AHSG (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-10-29). Common (popmax 33.5%, afr) — too common for a highly-penetrant pathogenic allele; Associated with AHSG-related disorder.

What condition is associated with AHSG p.Leu13= (c.39C>G)?

AHSG p.Leu13= (c.39C>G) is associated with AHSG-related disorder (ClinVar).

AHSG p.Leu13=

Q: How common is AHSG p.Leu13= (c.39C>G) in the general population?

AHSG p.Leu13= (c.39C>G) is common (popmax 33.5%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.39C>G · rs4831 · VCV3058930

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 33.5%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

AHSG-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.57	GERP -0.54, phastCons 1
Overall
CADD	9.9	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 33.5% African / African-American · 25,064/74,886 alleles

Filtering AF 33.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 33%

Overall 15.3% 247,675/1,613,722 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	33.5%	3
Middle Eastern	24.3%	4
Ashkenazi Jewishnot grpmax-eligible	24%	4
South Asian	20.7%	5
Remaining individualsnot grpmax-eligible	16.5%	6
Admixed American	14.3%	7
East Asian	14.1%	7
European (non-Finnish)	13.9%	7
Finnishnot grpmax-eligible	9.28%	11
Amishnot grpmax-eligible	5.81%	17

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: AHSG
Protein: p.Leu13=
Coding: c.39C>G
MANE Select: NM_001622
dbSNP: rs4831
Type: single nucleotide variant
Location: chr3:186613180 (GRCh38)
Gene constraint: LOEUF 1.042 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.59

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

Disease context

AHSG-related disorder

Similar variants

AHSG c.214-903G>A Benign same condition
AHSG c.*7C>A Benign same condition
AHSG p.Leu309= Benign same condition
AHSG p.Val342Met Uncertain significance ★★ ⚠ same type
AHSG p.Ala170= Benign/Likely benign ★★ same type
AHSG p.Arg317Cys Benign ★★ ⚠ same type
AHSG p.Met248Thr Benign ★★ same type
AHSG p.Ser256Thr Benign ★★ 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/ahsg-p-leu13 (accessed [today's date]).

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