Is IHH p.Phe367= (c.1101T>C) pathogenic?

IHH p.Phe367= (c.1101T>C) is classified Uncertain significance in IHH (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-12). Very rare (popmax 6.2e-05%); Associated with brachydactyly type A1.

What condition is associated with IHH p.Phe367= (c.1101T>C)?

IHH p.Phe367= (c.1101T>C) is associated with brachydactyly type A1 (ClinVar).

How common is IHH p.Phe367= (c.1101T>C) in the general population?

IHH p.Phe367= (c.1101T>C) is very rare (popmax 6.2e-05%) (gnomAD).

IHH p.Phe367=

c.1101T>C · rs886055650 · VCV334433

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 6.2e-05%)

Conditions

brachydactyly type A1

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 1.5	GERP -2.4, phastCons 1
Overall
CADD	6.358	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.2e-05%

Overall 6.2e-05% 1/1,613,276 alleles · very rare exomes 1/1,460,928 · genomes 0/152,348 · joint denominator

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.Phe367=
Coding: c.1101T>C
MANE Select: NM_002181
dbSNP: rs886055650
Type: single nucleotide variant
Location: chr2:219055342 (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 A1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

IHH p.Asp100Asn 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.Val304Leu Uncertain significance ★★ ⚠ same condition
IHH c.315+8C>T Benign/Likely benign ★★ 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-phe367 (accessed [today's date]).

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