Is AHCTF1 p.Ser10Arg (c.28A>C) pathogenic?

AHCTF1 p.Ser10Arg (c.28A>C) is classified Uncertain significance in AHCTF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-17). AlphaMissense: likely pathogenic (0.8394); Very rare (popmax 0.00134%, afr).

How common is AHCTF1 p.Ser10Arg (c.28A>C) in the general population?

AHCTF1 p.Ser10Arg (c.28A>C) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about AHCTF1 p.Ser10Arg (c.28A>C)?

AlphaMissense predicts likely pathogenic (score 0.8394) — an in-silico prediction, not a clinical call.

AHCTF1 p.Ser10Arg

c.28A>C · VCV3276878

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8394 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8394	likely pathogenic · top 8% in AHCTF1
REVEL	0.199	benign-leaning
SaProt	LLR -9.54	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 4.1	GERP 0.27, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 2,076 bp · p 0.076 · regional, not allelic
Overall
CADD	24.1	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 0.00134% African / African-American · 1/74,900 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000248% 4/1,612,606 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,900
European (non-Finnish)	0.000254%	393,151

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: AHCTF1
Protein: p.Ser10Arg
Coding: c.28A>C
MANE Select: NM_001323342
Type: single nucleotide variant
Location: chr1:246918343 (GRCh38)
Gene constraint: LOEUF 0.142 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 55.33 · 2 PDB
Residue 10: 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-ser10arg (accessed [today's date]).

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