Is AHCTF1 p.Pro1040Arg (c.3119C>G) pathogenic?

AHCTF1 p.Pro1040Arg (c.3119C>G) is classified Uncertain significance in AHCTF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-13). AlphaMissense: ambiguous (0.4548); Absent from gnomAD v4.1.

How common is AHCTF1 p.Pro1040Arg (c.3119C>G) in the general population?

AHCTF1 p.Pro1040Arg (c.3119C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AHCTF1 p.Pro1040Arg (c.3119C>G)?

AlphaMissense predicts ambiguous (score 0.4548) — an in-silico prediction, not a clinical call.

AHCTF1 p.Pro1040Arg

c.3119C>G · VCV4254148

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4548 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4548	ambiguous
REVEL	0.262	benign-leaning
SaProt	LLR -6.51	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 10	GERP 1.9, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 27 kb · p 0.002 · regional, not allelic
Overall
CADD	24.6	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: AHCTF1
Protein: p.Pro1040Arg
Coding: c.3119C>G
MANE Select: NM_001323342
Type: single nucleotide variant
Location: chr1:246867781 (GRCh38)
Gene constraint: LOEUF 0.142 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 55.33 · 2 PDB
Residue 1040: the 'important for nuclear localization' region; the 'disordered' 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-pro1040arg (accessed [today's date]).

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