Is ASPH p.Asp173fs (c.518del) pathogenic?

ASPH p.Asp173fs (c.518del) is classified Conflicting classifications of pathogenicity in ASPH (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-11-09). Low-frequency (popmax 1.76%, afr).

How common is ASPH p.Asp173fs (c.518del) in the general population?

ASPH p.Asp173fs (c.518del) is low-frequency (popmax 1.76%, afr) (gnomAD).

ASPH p.Asp173fs

c.518del · rs80163539 · VCV422209

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

low-frequency (popmax 1.76%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 6 of 25
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -2.3	GERP -3.6
Overall
CADD	19.59	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.76% African / African-American · 1,318/75,040 alleles

Filtering AF 1.68% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.65%

Overall 0.0961% 1,551/1,613,976 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.76%	57
Admixed American	0.127%	790
Remaining individualsnot grpmax-eligible	0.115%	868
Middle Eastern	0.099%	1,010
European (non-Finnish)	0.00636%	15,732
South Asian	0.00439%	22,763

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: ASPH
Protein: p.Asp173fs
Coding: c.518del
MANE Select: NM_004318
dbSNP: rs80163539
Type: Deletion
Location: chr8:61646851 (GRCh38)
Gene constraint: LOEUF 1.011 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 72.34 · 43 PDB

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

Similar variants

ASPH p.Asn637fs Pathogenic ★ same type
ASPH p.Asp720fs Likely pathogenic ★ same type
ASPH p.Gly714fs Likely pathogenic ★ same type
ASPH p.Ile497fs Likely pathogenic ★ same type
ASPH p.Leu465fs Pathogenic ★ same type
ASPH p.Lys391fs Likely pathogenic ★ same type
ASPH p.Tyr583fs Likely pathogenic ★ same type
ASPH c.1062+81del Likely 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/asph-p-asp173fs (accessed [today's date]).

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