Is AHDC1 p.Pro83Arg (c.248C>G) pathogenic?

AHDC1 p.Pro83Arg (c.248C>G) is classified Benign/Likely benign in AHDC1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-12-28). AlphaMissense: likely benign (0.0973); Ultra-rare (popmax 0.0669%, afr).

How common is AHDC1 p.Pro83Arg (c.248C>G) in the general population?

AHDC1 p.Pro83Arg (c.248C>G) is ultra-rare (popmax 0.0669%, afr) (gnomAD).

What do computational predictors say about AHDC1 p.Pro83Arg (c.248C>G)?

AlphaMissense predicts likely benign (score 0.0973) — an in-silico prediction, not a clinical call.

AHDC1 p.Pro83Arg

c.248C>G · rs751027836 · VCV1175451

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0973 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0669%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0973	likely benign
REVEL	0.085	moderately benign-leaning
SaProt	LLR -6.67	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 6.1	GERP -0.57, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 328 bp · p 0.067 · regional, not allelic
Overall
CADD	18.52	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 0.0669% African / African-American · 50/74,734 alleles

Filtering AF 0.0521% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0468%

Overall 0.00323% 52/1,608,788 alleles · ultra-rare exomes 15/1,456,884 · genomes 37/151,904 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0669%	1,495
Admixed American	0.00334%	29,923

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.Pro83Arg
Coding: c.248C>G
MANE Select: NM_001371928
dbSNP: rs751027836
Type: single nucleotide variant
Location: chr1:27551868 (GRCh38)
Gene constraint: LOEUF 0.168 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 38.82
Residue 83: the 'disordered' region

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

Similar variants

AHDC1 p.Pro83= Likely benign ★★ same residue
AHDC1 p.Pro83Leu Benign ★ same residue
AHDC1 p.Arg1272Ter Pathogenic ★★ same type
AHDC1 p.Arg151Ter Pathogenic/Likely pathogenic ★★ same type
AHDC1 p.Arg587Ter Pathogenic ★★ same type
AHDC1 p.Arg688Ter Pathogenic ★★ same type
AHDC1 p.Arg789Ter Pathogenic ★★ same type
AHDC1 p.Arg925Ter Pathogenic/Likely pathogenic ★★ 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/ahdc1-p-pro83arg (accessed [today's date]).

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