Is IHH p.Pro273= (c.819C>T) pathogenic?

IHH p.Pro273= (c.819C>T) is classified Benign/Likely benign in IHH (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-01). Low-frequency (popmax 2.91%, afr); Associated with brachydactyly type A1A.

What condition is associated with IHH p.Pro273= (c.819C>T)?

IHH p.Pro273= (c.819C>T) is associated with brachydactyly type A1A, brachydactyly type A1, acrocapitofemoral dysplasia (ClinVar).

How common is IHH p.Pro273= (c.819C>T) in the general population?

IHH p.Pro273= (c.819C>T) is low-frequency (popmax 2.91%, afr) (gnomAD).

IHH p.Pro273=

c.819C>T · rs61747697 · VCV334437

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.91%, afr)

Conditions

brachydactyly type A1A

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -12	GERP -5
Overall
CADD	0.02	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.91% African / African-American · 2,181/75,056 alleles

Filtering AF 2.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.76%

Overall 0.166% 2,680/1,614,024 alleles · low-frequency exomes 1,392/1,461,664 · genomes 1,288/152,360 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.91%	34
Middle Eastern	0.594%	168
Admixed American	0.22%	455
Remaining individualsnot grpmax-eligible	0.213%	470
South Asian	0.0231%	4,338
European (non-Finnish)	0.0149%	6,704
East Asian	0.00223%	44,880

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: IHH
Protein: p.Pro273=
Coding: c.819C>T
MANE Select: NM_002181
dbSNP: rs61747697
Type: single nucleotide variant
Location: chr2:219055624 (GRCh38)
Gene constraint: LOEUF 0.544 · pLI 0.94 (gnomAD)
Structure: AlphaFold pLDDT 84.84 · 8 PDB

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

Disease context

brachydactyly type A1A — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: brachydactyly type A1 acrocapitofemoral dysplasia

Similar variants

IHH p.Asp100Asn Pathogenic ★★ same condition
IHH p.Met1Val Likely pathogenic ★★ same condition
IHH c.*423G>A Uncertain significance ★★ same condition
IHH p.Arg217Cys Uncertain significance ★★ ⚠ same condition
IHH p.Arg267Gly Uncertain significance ★★ ⚠ same condition
IHH p.Arg390His Uncertain significance ★★ ⚠ same condition
IHH p.Asn161Ser Uncertain significance ★★ ⚠ same condition
IHH p.Thr284Met Uncertain significance ★★ ⚠ 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/ihh-p-pro273 (accessed [today's date]).

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