Is HAND1 p.Pro62= (c.186G>T) pathogenic?

HAND1 p.Pro62= (c.186G>T) is classified Likely benign in HAND1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-07-05). Very rare (popmax 0.00187%, nfe); Associated with hypoplastic left heart syndrome.

What condition is associated with HAND1 p.Pro62= (c.186G>T)?

HAND1 p.Pro62= (c.186G>T) is associated with hypoplastic left heart syndrome (ClinVar).

How common is HAND1 p.Pro62= (c.186G>T) in the general population?

HAND1 p.Pro62= (c.186G>T) is very rare (popmax 0.00187%, nfe) (gnomAD).

HAND1 p.Pro62=

c.186G>T · rs748732968 · VCV2056807

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00187%, nfe)

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 -3.1	GERP -4.1
Overall
CADD	8.305	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00187% European (non-Finnish) · 22/1,175,650 alleles

Filtering AF 0.00122% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00105%

Overall 0.00145% 23/1,589,860 alleles · very rare exomes 19/1,440,526 · genomes 4/149,334 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00187%	53,439
Remaining individualsnot grpmax-eligible	0.00162%	61,786

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: HAND1
Protein: p.Pro62=
Coding: c.186G>T
MANE Select: NM_004821
dbSNP: rs748732968
Type: single nucleotide variant
Location: chr5:154477823 (GRCh38)
Gene constraint: LOEUF 1.188 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.87
Residue 62: 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.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
HAND1 p.Pro188Ala 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-pro62 (accessed [today's date]).

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