Is CLUAP1 p.Lys307Gln (c.919A>C) pathogenic?

CLUAP1 p.Lys307Gln (c.919A>C) is classified Benign in CLUAP1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-02-01). AlphaMissense: likely benign (0.0952); Low-frequency (popmax 4.85%, afr).

How common is CLUAP1 p.Lys307Gln (c.919A>C) in the general population?

CLUAP1 p.Lys307Gln (c.919A>C) is low-frequency (popmax 4.85%, afr) (gnomAD).

What do computational predictors say about CLUAP1 p.Lys307Gln (c.919A>C)?

AlphaMissense predicts likely benign (score 0.0952) — an in-silico prediction, not a clinical call.

CLUAP1 p.Lys307Gln

c.919A>C · rs35603863 · VCV711989

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0952 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 4.85%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0952	likely benign
REVEL	0.108	moderately benign-leaning
SaProt	LLR -7.13	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>T here scores Δ0.34 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.6	GERP 0.093, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 35 kb · p 0.32 · regional, not allelic
Overall
CADD	19.67	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 4.85% African / African-American · 3,616/74,546 alleles

Filtering AF 4.72% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.66%

Overall 0.255% 4,089/1,606,140 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	4.85%	21
Admixed American	0.349%	287
Remaining individualsnot grpmax-eligible	0.343%	291
Middle Eastern	0.182%	549
South Asian	0.0134%	7,446
European (non-Finnish)	0.00297%	33,648

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.Lys307Gln
Coding: c.919A>C
MANE Select: NM_015041
dbSNP: rs35603863
Type: single nucleotide variant
Location: chr16:3526475 (GRCh38)
Gene constraint: LOEUF 1.23 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.02
Residue 307: the 'disordered' region

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-lys307gln (accessed [today's date]).

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