Is ASPHD2 p.Asn264Ser (c.791A>G) pathogenic?

ASPHD2 p.Asn264Ser (c.791A>G) is classified Uncertain significance in ASPHD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-05). AlphaMissense: ambiguous (0.3875); Very rare (popmax 0.0022%, sas).

How common is ASPHD2 p.Asn264Ser (c.791A>G) in the general population?

ASPHD2 p.Asn264Ser (c.791A>G) is very rare (popmax 0.0022%, sas) (gnomAD).

What do computational predictors say about ASPHD2 p.Asn264Ser (c.791A>G)?

AlphaMissense predicts ambiguous (score 0.3875) — an in-silico prediction, not a clinical call.

ASPHD2 p.Asn264Ser

c.791A>G · rs2517824744 · VCV3130458

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3875 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3875	ambiguous
REVEL	0.235	benign-leaning
SaProt	LLR -9.11	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.1, phastCons 1
Regional constraint	o/e 0.65	unconstrained · MANE · 8,962 bp · p 2.7e-07 · regional, not allelic
Overall
CADD	24.4	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 0.0022% South Asian · 2/91,080 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.000137% 2/1,461,868 alleles · very rare

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.Asn264Ser
Coding: c.791A>G
MANE Select: NM_020437
dbSNP: rs2517824744
Type: single nucleotide variant
Location: chr22:26434406 (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.Asn90Ser 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-asn264ser (accessed [today's date]).

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