Is HAND1 p.Pro188= (c.564T>C) pathogenic?

HAND1 p.Pro188= (c.564T>C) is classified Likely benign in HAND1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-02). Absent from gnomAD v4.1; Associated with hypoplastic left heart syndrome.

What condition is associated with HAND1 p.Pro188= (c.564T>C)?

HAND1 p.Pro188= (c.564T>C) is associated with hypoplastic left heart syndrome (ClinVar).

How common is HAND1 p.Pro188= (c.564T>C) in the general population?

HAND1 p.Pro188= (c.564T>C) is absent from gnomAD v4.1 (gnomAD).

HAND1 p.Pro188=

c.564T>C · rs1561710559 · VCV1623814

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hypoplastic left heart syndrome

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 5.4	GERP 1, phastCons 1
Overall
CADD	13.58	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: HAND1
Protein: p.Pro188=
Coding: c.564T>C
MANE Select: NM_004821
dbSNP: rs1561710559
Type: single nucleotide variant
Location: chr5:154475890 (GRCh38)
Gene constraint: LOEUF 1.188 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.87
Residue 188: the 'disordered' region

Full HAND1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hypoplastic left heart syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

HAND1 p.Pro188Ala Uncertain significance ★★ ⚠ same residue
HAND1 p.Ala68Pro Uncertain significance ★★ ⚠ same condition
HAND1 p.Arg91Gly Uncertain significance ★★ ⚠ same condition
HAND1 p.Gln43Arg Uncertain significance ★★ ⚠ same condition
HAND1 p.Glu103Gly Uncertain significance ★★ ⚠ same condition
HAND1 p.Gly203Ala Uncertain significance ★★ ⚠ same condition
HAND1 p.Leu3Val Uncertain significance ★★ ⚠ same condition
HAND1 p.Pro125Arg 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/hand1-p-pro188 (accessed [today's date]).

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