Is CLUAP1 p.Ala68Ser (c.202G>T) pathogenic?

CLUAP1 p.Ala68Ser (c.202G>T) is classified Benign in CLUAP1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-24). AlphaMissense: likely benign (0.1787); Common (popmax 7.66%, afr) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about CLUAP1 p.Ala68Ser (c.202G>T)?

AlphaMissense predicts likely benign (score 0.1787) — an in-silico prediction, not a clinical call.

CLUAP1 p.Ala68Ser

Q: How common is CLUAP1 p.Ala68Ser (c.202G>T) in the general population?

CLUAP1 p.Ala68Ser (c.202G>T) is common (popmax 7.66%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.202G>T · rs34115694 · VCV776970

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1787 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 7.66%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1787	likely benign
REVEL	0.149	moderately benign-leaning
SaProt	LLR -5.62	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.4	GERP 2.4, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 35 kb · p 0.32 · regional, not allelic
Overall
CADD	21.1	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 7.66% African / African-American · 5,746/75,006 alleles

Filtering AF 7.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.43%

Overall 0.415% 6,699/1,613,752 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	7.66%	13
Remaining individualsnot grpmax-eligible	0.512%	195
Admixed American	0.511%	196
Ashkenazi Jewishnot grpmax-eligible	0.473%	211
Middle Eastern	0.247%	404
South Asian	0.0242%	4,140
European (non-Finnish)	0.0125%	8,025
Finnishnot grpmax-eligible	0.00312%	32,009

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.Ala68Ser
Coding: c.202G>T
MANE Select: NM_015041
dbSNP: rs34115694
Type: single nucleotide variant
Location: chr16:3506398 (GRCh38)
Gene constraint: LOEUF 1.23 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.02
Residue 68: a UniProt-annotated variant site (in)

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-ala68ser (accessed [today's date]).

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