Is ASPH p.Thr340= (c.1020T>C) pathogenic?

ASPH p.Thr340= (c.1020T>C) is classified Benign in ASPH (ClinVar, Single submitter, 2 submitters; last evaluated 2024-11-04). Rare (popmax 0.148%, nfe).

How common is ASPH p.Thr340= (c.1020T>C) in the general population?

ASPH p.Thr340= (c.1020T>C) is rare (popmax 0.148%, nfe) (gnomAD).

ASPH p.Thr340=

c.1020T>C · rs149828220 · VCV787621

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.148%, nfe)

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 0.24	GERP -2.5, phastCons 0.38
Overall
CADD	5.209	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.148% European (non-Finnish) · 1,718/1,164,686 alleles

Filtering AF 0.142% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.139%

Overall 0.129% 2,046/1,583,626 alleles · rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.475%	210
European (non-Finnish)grpmax	0.148%	678
Finnishnot grpmax-eligible	0.135%	740
Remaining individualsnot grpmax-eligible	0.135%	740
African / African-American	0.0191%	5,237
Admixed American	0.0127%	7,844

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Thr340=
Coding: c.1020T>C
MANE Select: NM_004318
dbSNP: rs149828220
Type: single nucleotide variant
Location: chr8:61583986 (GRCh38)
Gene constraint: LOEUF 1.011 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 72.34 · 43 PDB
Residue 340: an α-helix

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

Similar variants

ASPH p.Arg735Trp Likely pathogenic ★★ same type
ASPH p.Tyr565Ter Pathogenic/Likely pathogenic ★★ same type
ASPH p.Arg425Cys Uncertain significance ★★ ⚠ same type
ASPH p.Arg753His Uncertain significance ★★ ⚠ same type
ASPH p.Glu506Val Uncertain significance ★★ ⚠ same type
ASPH p.Leu433Arg Uncertain significance ★★ ⚠ same type
ASPH p.Ser299Asn Uncertain significance ★★ ⚠ same type
ASPH p.Val214Met 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/asph-p-thr340 (accessed [today's date]).

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