Is ASPHD2 p.Cys247Gly (c.739T>G) pathogenic?

ASPHD2 p.Cys247Gly (c.739T>G) is classified Uncertain significance in ASPHD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-02). AlphaMissense: likely pathogenic (0.9235); Absent from gnomAD v4.1.

How common is ASPHD2 p.Cys247Gly (c.739T>G) in the general population?

ASPHD2 p.Cys247Gly (c.739T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ASPHD2 p.Cys247Gly (c.739T>G)?

AlphaMissense predicts likely pathogenic (score 0.9235) — an in-silico prediction, not a clinical call.

ASPHD2 p.Cys247Gly

c.739T>G · rs2517824677 · VCV2615244

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9235 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9235	likely pathogenic
REVEL	0.718	pathogenic-leaning
SaProt	LLR -12.79	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	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	29.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ASPHD2
Protein: p.Cys247Gly
Coding: c.739T>G
MANE Select: NM_020437
dbSNP: rs2517824677
Type: single nucleotide variant
Location: chr22:26434354 (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.Cys247Tyr Uncertain significance ★ ⚠ same residue
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

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-cys247gly (accessed [today's date]).

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