Is CLUAP1 p.Leu193Phe (c.579G>C) pathogenic?

CLUAP1 p.Leu193Phe (c.579G>C) is classified Uncertain significance in CLUAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-17). AlphaMissense: likely benign (0.1239); Ultra-rare (popmax 0.0908%, sas).

How common is CLUAP1 p.Leu193Phe (c.579G>C) in the general population?

CLUAP1 p.Leu193Phe (c.579G>C) is ultra-rare (popmax 0.0908%, sas) (gnomAD).

What do computational predictors say about CLUAP1 p.Leu193Phe (c.579G>C)?

AlphaMissense predicts likely benign (score 0.1239) — an in-silico prediction, not a clinical call.

CLUAP1 p.Leu193Phe

c.579G>C · rs768886313 · VCV943604

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1239 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0908%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1239	likely benign
REVEL	0.167	moderately benign-leaning
SaProt	LLR -10.53	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>A here scores Δ0.38 · evaluated, not missing
Pangolin	Δ0.25	loss · gain 0.01 · SpliceAI below 0.2 · independent
Constraint at this position
Conservation	phyloP 9.7	GERP 2.5, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 35 kb · p 0.32 · regional, not allelic
Overall
CADD	33.0	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 0.0908% South Asian · 77/84,794 alleles

Filtering AF 0.0744% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0685%

Overall 0.00551% 87/1,578,458 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0908%	1,101
Middle Eastern	0.0333%	3,003
Remaining individualsnot grpmax-eligible	0.00491%	20,348
East Asian	0.00229%	43,578
African / African-American	0.00138%	72,382
European (non-Finnish)	0.000257%	389,197

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.Leu193Phe
Coding: c.579G>C
MANE Select: NM_015041
dbSNP: rs768886313
Type: single nucleotide variant
Location: chr16:3515591 (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.Leu193= Likely benign ★ same residue
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

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-leu193phe (accessed [today's date]).

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