Is CLUAP1 p.Val196Phe (c.586G>T) pathogenic?

CLUAP1 p.Val196Phe (c.586G>T) is classified Benign in CLUAP1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-01). AlphaMissense: likely benign (0.2985); Low-frequency (popmax 2.3%, afr).

How common is CLUAP1 p.Val196Phe (c.586G>T) in the general population?

CLUAP1 p.Val196Phe (c.586G>T) is low-frequency (popmax 2.3%, afr) (gnomAD).

What do computational predictors say about CLUAP1 p.Val196Phe (c.586G>T)?

AlphaMissense predicts likely benign (score 0.2985) — an in-silico prediction, not a clinical call.

CLUAP1 p.Val196Phe

c.586G>T · rs35065818 · VCV1164359

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2985 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.3%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2985	likely benign
REVEL	0.087	moderately benign-leaning
SaProt	LLR -12.93	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.3	GERP 1.2, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 35 kb · p 0.32 · regional, not allelic
Overall
CADD	25.8	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.3% African / African-American · 1,698/73,924 alleles

Filtering AF 2.21% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.17%

Overall 0.264% 4,229/1,600,800 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.3%	44
Middle Eastern	1.37%	73
Admixed American	0.436%	229
Remaining individualsnot grpmax-eligible	0.354%	283
South Asian	0.261%	384
European (non-Finnish)	0.145%	690
Ashkenazi Jewishnot grpmax-eligible	0.12%	832
Finnishnot grpmax-eligible	0.0266%	3,755

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: CLUAP1
Protein: p.Val196Phe
Coding: c.586G>T
MANE Select: NM_015041
dbSNP: rs35065818
Type: single nucleotide variant
Location: chr16:3519909 (GRCh38)
Gene constraint: LOEUF 1.23 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.02

Full CLUAP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CLUAP1 p.Ala152Glu Uncertain significance ★★ ⚠ same type
CLUAP1 p.Ala188Gly Uncertain significance ★★ ⚠ same type
CLUAP1 p.Ala339Thr Uncertain significance ★★ ⚠ same type
CLUAP1 p.Arg20Gln Uncertain significance ★★ ⚠ same type
CLUAP1 p.Arg228Gln Uncertain significance ★★ ⚠ same type
CLUAP1 p.Arg304His Uncertain significance ★★ ⚠ same type
CLUAP1 p.Arg332Gln Uncertain significance ★★ ⚠ same type
CLUAP1 p.Asn296Lys 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/cluap1-p-val196phe (accessed [today's date]).

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