Is ASPHD2 p.Asn90Ser (c.269A>G) pathogenic?

ASPHD2 p.Asn90Ser (c.269A>G) is classified Uncertain significance in ASPHD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-22). AlphaMissense: likely benign (0.0628); Very rare (popmax 0.0072%, nfe).

How common is ASPHD2 p.Asn90Ser (c.269A>G) in the general population?

ASPHD2 p.Asn90Ser (c.269A>G) is very rare (popmax 0.0072%, nfe) (gnomAD).

What do computational predictors say about ASPHD2 p.Asn90Ser (c.269A>G)?

AlphaMissense predicts likely benign (score 0.0628) — an in-silico prediction, not a clinical call.

ASPHD2 p.Asn90Ser

c.269A>G · VCV3790165

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0628 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0072%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0628	likely benign
REVEL	0.017	moderately benign-leaning
SaProt	LLR -4.95	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 1.1	GERP 1.5, phastCons 0.001
Regional constraint	o/e 0.87	unconstrained · MANE · 548 bp · p 0.03 · regional, not allelic
Overall
CADD	15.73	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0072% European (non-Finnish) · 85/1,179,984 alleles

Filtering AF 0.00596% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00549%

Overall 0.00539% 87/1,613,356 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0072%	13,882
Finnishnot grpmax-eligible	0.00157%	63,608
South Asian	0.0011%	91,070

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: ASPHD2
Protein: p.Asn90Ser
Coding: c.269A>G
MANE Select: NM_020437
Type: single nucleotide variant
Location: chr22:26433884 (GRCh38)
Gene constraint: LOEUF 0.547 · pLI 0.92 (gnomAD)
Structure: AlphaFold pLDDT 81.08

Full ASPHD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ASPHD2 p.Ala47Val Uncertain significance ★ ⚠ same type
ASPHD2 p.Arg154Trp Uncertain significance ★ ⚠ same type
ASPHD2 p.Arg159Gln Uncertain significance ★ ⚠ same type
ASPHD2 p.Arg341Trp Uncertain significance ★ ⚠ same type
ASPHD2 p.Arg43Lys Uncertain significance ★ ⚠ same type
ASPHD2 p.Arg84Trp Uncertain significance ★ ⚠ same type
ASPHD2 p.Asn129Ser Uncertain significance ★ ⚠ same type
ASPHD2 p.Asn264Ser 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/asphd2-p-asn90ser (accessed [today's date]).

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