Is CLUH p.Asp376= (c.1128C>T) pathogenic?

CLUH p.Asp376= (c.1128C>T) is classified Benign in CLUH (ClinVar, Single submitter, 1 submitter; last evaluated 2018-02-26). Rare (popmax 0.467%, afr).

How common is CLUH p.Asp376= (c.1128C>T) in the general population?

CLUH p.Asp376= (c.1128C>T) is rare (popmax 0.467%, afr) (gnomAD).

CLUH p.Asp376=

c.1128C>T · rs73976569 · VCV727263

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.467%, afr)

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 -6.2	GERP -4.7
Overall
CADD	0.163	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.467% African / African-American · 338/72,426 alleles

Filtering AF 0.426% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.41%

Overall 0.0249% 384/1,539,652 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.467%	214
Remaining individualsnot grpmax-eligible	0.0338%	2,961
Admixed American	0.0318%	3,145
Middle Eastern	0.0176%	5,696
South Asian	0.00512%	19,528
European (non-Finnish)	0.000523%	191,255

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: CLUH
Protein: p.Asp376=
Coding: c.1128C>T
MANE Select: NM_001366661
dbSNP: rs73976569
Type: single nucleotide variant
Location: chr17:2700723 (GRCh38)
Gene constraint: LOEUF 0.799 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.11
Residue 376: the clu domain

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

Similar variants

CLUH p.Ala671Val Benign ★★ same type
CLUH p.Ala700= Likely benign ★★ same type
CLUH p.Glu1228= Likely benign ★★ same type
CLUH p.Thr201= Benign ★★ same type
CLUH c.1025+1G>A Uncertain significance ★ same type
CLUH p.Ala1076Thr Uncertain significance ★ ⚠ same type
CLUH p.Ala1257Ser Uncertain significance ★ ⚠ same type
CLUH p.Ala1320Gly Uncertain significance ★ ⚠ same type

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/cluh-p-asp376 (accessed [today's date]).

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