Is AHCTF1 p.Asp3Val (c.8A>T) pathogenic?

AHCTF1 p.Asp3Val (c.8A>T) is classified Uncertain significance in AHCTF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-04). AlphaMissense: likely benign (0.3217); Absent from gnomAD v4.1.

How common is AHCTF1 p.Asp3Val (c.8A>T) in the general population?

AHCTF1 p.Asp3Val (c.8A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AHCTF1 p.Asp3Val (c.8A>T)?

AlphaMissense predicts likely benign (score 0.3217) — an in-silico prediction, not a clinical call.

AHCTF1 p.Asp3Val

c.8A>T · rs2527631955 · VCV2616417

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3217 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3217	likely benign
REVEL	0.279	benign-leaning
SaProt	LLR -6.21	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 6.2	GERP 1.4, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 2,076 bp · p 0.076 · regional, not allelic
Overall
CADD	24.6	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

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: AHCTF1
Protein: p.Asp3Val
Coding: c.8A>T
MANE Select: NM_001323342
dbSNP: rs2527631955
Type: single nucleotide variant
Location: chr1:246918363 (GRCh38)
Gene constraint: LOEUF 0.142 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 55.33 · 2 PDB
Residue 3: the 'necessary for cytoplasmic localization' region; the 'seven-bladed beta propeller repeats' region

Full AHCTF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AHCTF1 c.-8+263C>G Uncertain significance ★ same type
AHCTF1 p.Ala1247Thr Uncertain significance ★ ⚠ same type
AHCTF1 p.Ala1346Val Uncertain significance ★ ⚠ same type
AHCTF1 p.Ala1392Val Uncertain significance ★ ⚠ same type
AHCTF1 p.Ala1537Val Uncertain significance ★ ⚠ same type
AHCTF1 p.Ala1667Val Uncertain significance ★ ⚠ same type
AHCTF1 p.Ala1763Gly Uncertain significance ★ ⚠ same type
AHCTF1 p.Ala195Pro 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/ahctf1-p-asp3val (accessed [today's date]).

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