Is ASPH p.Pro282Ser (c.844C>T) pathogenic?

ASPH p.Pro282Ser (c.844C>T) is classified Conflicting classifications of pathogenicity in ASPH (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2026-01-24). AlphaMissense: likely benign (0.0648); Rare (popmax 0.605%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ASPH p.Pro282Ser (c.844C>T)?

ASPH p.Pro282Ser (c.844C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ASPH p.Pro282Ser (c.844C>T) in the general population?

ASPH p.Pro282Ser (c.844C>T) is rare (popmax 0.605%, nfe) (gnomAD).

What do computational predictors say about ASPH p.Pro282Ser (c.844C>T)?

AlphaMissense predicts likely benign (score 0.0648) — an in-silico prediction, not a clinical call.

ASPH p.Pro282Ser

c.844C>T · rs141197241 · VCV718344

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

AlphaMissense

likely benign

0.0648 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.605%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0648	likely benign
REVEL	0.049	moderately benign-leaning
SaProt	LLR -6.37	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 0.68	GERP -0.58, phastCons 0.88
Regional constraint	o/e 1.00	unconstrained · MANE · 211 kb · p 0.99 · regional, not allelic
Overall
CADD	4.433	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 0.605% European (non-Finnish) · 7,122/1,177,620 alleles

Filtering AF 0.593% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.588%

Overall 0.477% 7,666/1,607,884 alleles · rare exomes 7,152/1,455,634 · genomes 514/152,250 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.605%	165
Remaining individualsnot grpmax-eligible	0.328%	305
Finnishnot grpmax-eligible	0.266%	376
African / African-American	0.11%	910
Admixed American	0.0715%	1,400
South Asian	0.0457%	2,188
Middle Eastern	0.0333%	3,005
Ashkenazi Jewishnot grpmax-eligible	0.00681%	14,689
East Asian	0.00224%	44,656

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.Pro282Ser
Coding: c.844C>T
MANE Select: NM_004318
dbSNP: rs141197241
Type: single nucleotide variant
Location: chr8:61637992 (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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ASPH p.Arg753His Uncertain significance ★★ ⚠ same condition
ASPH p.Glu506Val Uncertain significance ★★ same condition
ASPH p.Leu433Arg Uncertain significance ★★ ⚠ same condition
ASPH p.Ser299Asn Uncertain significance ★★ ⚠ same condition
ASPH p.Val214Met Uncertain significance ★★ ⚠ same condition
ASPH p.Val462Met Uncertain significance ★★ ⚠ same condition
ASPH p.Val83Ala Uncertain significance ★★ ⚠ same condition
ASPH p.Met188Thr Likely benign ★★ same condition

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-pro282ser (accessed [today's date]).

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