Is CCDC88B p.Arg271Trp (c.811C>T) pathogenic?

CCDC88B p.Arg271Trp (c.811C>T) is classified Uncertain significance in CCDC88B (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-06). AlphaMissense: likely benign (0.1834); Very rare (popmax 0.0011%, sas).

How common is CCDC88B p.Arg271Trp (c.811C>T) in the general population?

CCDC88B p.Arg271Trp (c.811C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about CCDC88B p.Arg271Trp (c.811C>T)?

AlphaMissense predicts likely benign (score 0.1834) — an in-silico prediction, not a clinical call.

CCDC88B p.Arg271Trp

c.811C>T · rs2495890403 · VCV2317432

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1834 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1834	likely benign
REVEL	0.267	benign-leaning
SaProt	LLR -10.93	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 1.6	GERP 2.1, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 17 kb · p 0.0012 · 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 0.0011% South Asian · 1/90,520 alleles

Overall 0.000137% 2/1,456,362 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	90,520
European (non-Finnish)	8.49e-05%	1,178,412

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: CCDC88B
Protein: p.Arg271Trp
Coding: c.811C>T
MANE Select: NM_032251
dbSNP: rs2495890403
Type: single nucleotide variant
Location: chr11:64342129 (GRCh38)
Gene constraint: LOEUF 1.009 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.19

Full CCDC88B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC88B p.Arg271Gln Uncertain significance ★ ⚠ same residue
CCDC88B p.Arg328Ser Uncertain significance ★★ ⚠ same type
CCDC88B p.Leu1234= Benign ★★ same type
CCDC88B p.Ala1025Thr Uncertain significance ★ ⚠ same type
CCDC88B p.Ala1025Val Uncertain significance ★ ⚠ same type
CCDC88B p.Ala1059Val Uncertain significance ★ ⚠ same type
CCDC88B p.Ala1112Thr Uncertain significance ★ ⚠ same type
CCDC88B p.Ala1132Val 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/ccdc88b-p-arg271trp (accessed [today's date]).

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