Is ASPH p.Ala161Thr (c.481G>A) pathogenic?

ASPH p.Ala161Thr (c.481G>A) is classified Likely benign in ASPH (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-16). AlphaMissense: likely benign (0.0621); Rare (popmax 0.358%, afr).

How common is ASPH p.Ala161Thr (c.481G>A) in the general population?

ASPH p.Ala161Thr (c.481G>A) is rare (popmax 0.358%, afr) (gnomAD).

What do computational predictors say about ASPH p.Ala161Thr (c.481G>A)?

AlphaMissense predicts likely benign (score 0.0621) — an in-silico prediction, not a clinical call.

ASPH p.Ala161Thr

c.481G>A · rs77752382 · VCV2058082

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0621 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.358%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0621	likely benign
REVEL	0.032	moderately benign-leaning
SaProt	LLR -5.96	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.22	GERP -4.2
Regional constraint	o/e 1.00	unconstrained · MANE · 211 kb · p 0.99 · regional, not allelic
Overall
CADD	4.656	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 0.358% African / African-American · 268/74,960 alleles

Filtering AF 0.322% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.309%

Overall 0.0206% 333/1,612,650 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.358%	280
Admixed American	0.0534%	1,871
Remaining individualsnot grpmax-eligible	0.0272%	3,673
European (non-Finnish)	0.00136%	73,701

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.Ala161Thr
Coding: c.481G>A
MANE Select: NM_004318
dbSNP: rs77752382
Type: single nucleotide variant
Location: chr8:61651059 (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.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-ala161thr (accessed [today's date]).

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