Is ASPHD1 p.Ala375Val (c.1124C>T) pathogenic?

ASPHD1 p.Ala375Val (c.1124C>T) is classified Uncertain significance in ASPHD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-15). AlphaMissense: likely pathogenic (0.71); Absent from gnomAD v4.1.

How common is ASPHD1 p.Ala375Val (c.1124C>T) in the general population?

ASPHD1 p.Ala375Val (c.1124C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ASPHD1 p.Ala375Val (c.1124C>T)?

AlphaMissense predicts likely pathogenic (score 0.71) — an in-silico prediction, not a clinical call.

ASPHD1 p.Ala375Val

c.1124C>T · VCV4643536

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.71 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.71	likely pathogenic
REVEL	0.232	benign-leaning
SaProt	LLR -8.67	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 4,922 bp · p 0.049 · regional, not allelic
Overall
CADD	29.3	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

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: ASPHD1
Protein: p.Ala375Val
Coding: c.1124C>T
MANE Select: NM_181718
Type: single nucleotide variant
Location: chr16:29905848 (GRCh38)
Gene constraint: LOEUF 1.102 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.01

Full ASPHD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ASPHD1 p.Ala274Thr Uncertain significance ★ ⚠ same type
ASPHD1 p.Ala37Pro Uncertain significance ★ ⚠ same type
ASPHD1 p.Ala62Thr Uncertain significance ★ ⚠ same type
ASPHD1 p.Ala76Asp Uncertain significance ★ ⚠ same type
ASPHD1 p.Ala76Thr Uncertain significance ★ ⚠ same type
ASPHD1 p.Arg116Leu Uncertain significance ★ ⚠ same type
ASPHD1 p.Arg15Leu Uncertain significance ★ ⚠ same type
ASPHD1 p.Arg222Trp 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/asphd1-p-ala375val (accessed [today's date]).

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