Is HYCC1 p.Pro128= (c.384A>G) pathogenic?

HYCC1 p.Pro128= (c.384A>G) is classified Likely benign in HYCC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-07). Very rare (popmax 0.00536%, afr); Associated with leukodystrophy, hypomyelinating, 5.

What condition is associated with HYCC1 p.Pro128= (c.384A>G)?

HYCC1 p.Pro128= (c.384A>G) is associated with leukodystrophy, hypomyelinating, 5 (ClinVar).

How common is HYCC1 p.Pro128= (c.384A>G) in the general population?

HYCC1 p.Pro128= (c.384A>G) is very rare (popmax 0.00536%, afr) (gnomAD).

HYCC1 p.Pro128=

c.384A>G · rs773650463 · VCV2078310

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00536%, afr)

Conditions

leukodystrophy, hypomyelinating, 5

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.015	strongly benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.3	GERP -4.5, phastCons 1
Overall
CADD	8.11	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00536% African / African-American · 4/74,580 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.000313% 5/1,599,998 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00536%	18,645
East Asian	0.00224%	44,660

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: HYCC1
Protein: p.Pro128=
Coding: c.384A>G
MANE Select: NM_032581
dbSNP: rs773650463
Type: single nucleotide variant
Location: chr7:22977371 (GRCh38)
Structure: AlphaFold pLDDT 68.51 · 5 PDB

Full HYCC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

leukodystrophy, hypomyelinating, 5 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

HYCC1 c.414+1G>T Pathogenic/Likely pathogenic ★★ same condition
HYCC1 p.Gln49Ter Likely pathogenic ★★ same condition
HYCC1 p.Leu241Ter Pathogenic/Likely pathogenic ★★ same condition
HYCC1 c.831+5G>A Uncertain significance ★★ same condition
HYCC1 p.Ala256Pro Uncertain significance ★★ ⚠ same condition
HYCC1 p.Ala259Thr Uncertain significance ★★ ⚠ same condition
HYCC1 p.Ala88Ser Uncertain significance ★★ ⚠ same condition
HYCC1 p.Arg299Lys 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/hycc1-p-pro128 (accessed [today's date]).

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