Is CLUH p.Pro610Ala (c.1828C>G) pathogenic?

CLUH p.Pro610Ala (c.1828C>G) is classified Uncertain significance in CLUH (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-06). AlphaMissense: likely pathogenic (0.6146); Ultra-rare (popmax 0.0254%, afr).

How common is CLUH p.Pro610Ala (c.1828C>G) in the general population?

CLUH p.Pro610Ala (c.1828C>G) is ultra-rare (popmax 0.0254%, afr) (gnomAD).

What do computational predictors say about CLUH p.Pro610Ala (c.1828C>G)?

AlphaMissense predicts likely pathogenic (score 0.6146) — an in-silico prediction, not a clinical call.

CLUH p.Pro610Ala

c.1828C>G · VCV3494041

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6146 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0254%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6146	likely pathogenic
REVEL	0.662	pathogenic-leaning
SaProt	LLR -10.03	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.6, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 10 kb · p 0.061 · regional, not allelic
Overall
CADD	23.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P572A vs ClinVar P610A) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0254% African / African-American · 19/74,904 alleles

Filtering AF 0.0166% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0137%

Overall 0.00199% 32/1,605,228 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0254%	3,942
Admixed American	0.0117%	8,527
European (non-Finnish)	0.000509%	196,502

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.Pro610Ala
Coding: c.1828C>G
MANE Select: NM_001366661
Type: single nucleotide variant
Location: chr17:2698029 (GRCh38)
Gene constraint: LOEUF 0.799 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.11

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-pro610ala (accessed [today's date]).

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