Is HYCC1 p.Ser482= (c.1446C>T) pathogenic?

HYCC1 p.Ser482= (c.1446C>T) is classified Likely benign in HYCC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-13). Ultra-rare (popmax 0.0164%, mid); Associated with leukodystrophy, hypomyelinating, 5.

What condition is associated with HYCC1 p.Ser482= (c.1446C>T)?

HYCC1 p.Ser482= (c.1446C>T) is associated with leukodystrophy, hypomyelinating, 5 (ClinVar).

How common is HYCC1 p.Ser482= (c.1446C>T) in the general population?

HYCC1 p.Ser482= (c.1446C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

HYCC1 p.Ser482=

c.1446C>T · rs780099618 · VCV1643634

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Conditions

leukodystrophy, hypomyelinating, 5

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 -0.21	GERP -5.7, phastCons 0.006
Overall
CADD	7.005	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,082 alleles

Filtering AF 0.00544% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00381%

Overall 0.00143% 23/1,613,612 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,082
Admixed American	0.0117%	8,560
South Asian	0.00769%	13,011
African / African-American	0.00534%	18,717
European (non-Finnish)	0.000339%	294,956

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.Ser482=
Coding: c.1446C>T
MANE Select: NM_032581
dbSNP: rs780099618
Type: single nucleotide variant
Location: chr7:22945709 (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-ser482 (accessed [today's date]).

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