Is AHDC1 p.Pro75= (c.225A>G) pathogenic?

AHDC1 p.Pro75= (c.225A>G) is classified Benign/Likely benign in AHDC1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-21). Rare (popmax 0.117%, afr); Associated with AHDC1-related intellectual disability - obstructive sleep apnea - mild dysmorphism syndrome.

How common is AHDC1 p.Pro75= (c.225A>G) in the general population?

AHDC1 p.Pro75= (c.225A>G) is rare (popmax 0.117%, afr) (gnomAD).

AHDC1 p.Pro75=

Q: What condition is associated with AHDC1 p.Pro75= (c.225A>G)?

AHDC1 p.Pro75= (c.225A>G) is associated with AHDC1-related intellectual disability - obstructive sleep apnea - mild dysmorphism syndrome (ClinVar).

c.225A>G · rs377231405 · VCV744145

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.117%, afr)

Conditions

AHDC1-related intellectual disability - obstructive sleep apnea - mild dysmorphism syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.004	GERP 1.7, phastCons 0.95
Overall
CADD	9.241	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.117% African / African-American · 86/73,440 alleles

Filtering AF 0.097% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0897%

Overall 0.00619% 99/1,598,304 alleles · rare exomes 57/1,449,648 · genomes 42/148,656 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.117%	854
Remaining individualsnot grpmax-eligible	0.0178%	5,628
Middle Eastern	0.0166%	6,022
Admixed American	0.00169%	59,258

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: AHDC1
Protein: p.Pro75=
Coding: c.225A>G
MANE Select: NM_001371928
dbSNP: rs377231405
Type: single nucleotide variant
Location: chr1:27551891 (GRCh38)
Gene constraint: LOEUF 0.168 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 38.82
Residue 75: the 'disordered' region

Full AHDC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

AHDC1-related intellectual disability - obstructive sleep apnea - mild dysmorphism syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

AHDC1 p.Pro75Gln Uncertain significance ★ ⚠ same residue
AHDC1 p.Arg1272Ter Pathogenic ★★ same condition
AHDC1 p.Arg151Ter Pathogenic/Likely pathogenic ★★ same condition
AHDC1 p.Arg587Ter Pathogenic ★★ same condition
AHDC1 p.Arg688Ter Pathogenic ★★ same condition
AHDC1 p.Arg789Ter Pathogenic ★★ same condition
AHDC1 p.Arg925Ter Pathogenic/Likely pathogenic ★★ same condition
AHDC1 p.Gln332Ter Pathogenic ★★ same condition

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/ahdc1-p-pro75 (accessed [today's date]).

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