Is CLUH p.Ala671Val (c.2012C>T) pathogenic?

CLUH p.Ala671Val (c.2012C>T) is classified Benign in CLUH (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-06-15). AlphaMissense: likely benign (0.1485); Common (popmax 36.6%, eas) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about CLUH p.Ala671Val (c.2012C>T)?

AlphaMissense predicts likely benign (score 0.1485) — an in-silico prediction, not a clinical call.

CLUH p.Ala671Val

Q: How common is CLUH p.Ala671Val (c.2012C>T) in the general population?

CLUH p.Ala671Val (c.2012C>T) is common (popmax 36.6%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2012C>T · rs11078312 · VCV673336

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1485 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 36.6%, eas) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1485	likely benign
REVEL	0.31	indeterminate
SaProt	LLR -7.49	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.5, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 10 kb · p 0.061 · regional, not allelic
Overall
CADD	24.4	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM A633V vs ClinVar A671V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 36.6% East Asian · 16,396/44,760 alleles

Filtering AF 36.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 36%

Overall 13% 208,585/1,610,280 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	36.6%	3
South Asian	28.3%	4
Finnishnot grpmax-eligible	23%	4
Amishnot grpmax-eligible	22.1%	5
Admixed American	15.5%	6
Remaining individualsnot grpmax-eligible	14.1%	7
Middle Eastern	11.3%	9
European (non-Finnish)	10.8%	9
Ashkenazi Jewishnot grpmax-eligible	10.6%	9
African / African-American	3.88%	26

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.Ala671Val
Coding: c.2012C>T
MANE Select: NM_001366661
dbSNP: rs11078312
Type: single nucleotide variant
Location: chr17:2696892 (GRCh38)
Gene constraint: LOEUF 0.799 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.11
Residue 671: the 'disordered' region

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

Similar variants

CLUH p.Ala671Thr Uncertain significance ★ ⚠ same residue
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-ala671val (accessed [today's date]).

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