Is DRC2 p.Phe88Ser (c.263T>C) pathogenic?

DRC2 p.Phe88Ser (c.263T>C) is classified Uncertain significance in DRC2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-06-07). AlphaMissense: likely pathogenic (0.6726); Ultra-rare (popmax 0.0129%, nfe); Associated with Inborn genetic diseases.

What condition is associated with DRC2 p.Phe88Ser (c.263T>C)?

DRC2 p.Phe88Ser (c.263T>C) is associated with Inborn genetic diseases, primary ciliary dyskinesia 27 (ClinVar).

How common is DRC2 p.Phe88Ser (c.263T>C) in the general population?

DRC2 p.Phe88Ser (c.263T>C) is ultra-rare (popmax 0.0129%, nfe) (gnomAD).

What do computational predictors say about DRC2 p.Phe88Ser (c.263T>C)?

AlphaMissense predicts likely pathogenic (score 0.6726) — an in-silico prediction, not a clinical call.

DRC2 p.Phe88Ser

c.263T>C · rs148153593 · VCV1426614

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.6726 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0129%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6726	likely pathogenic · top 6% in DRC2
REVEL	0.467	indeterminate
SaProt	LLR -12.58	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 2.3, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 17 kb · p 0.19 · regional, not allelic
Overall
CADD	28.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0129% European (non-Finnish) · 152/1,179,762 alleles

Filtering AF 0.0112% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0106%

Overall 0.00992% 160/1,613,388 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0129%	7,762
African / African-American	0.00668%	14,968
Remaining individualsnot grpmax-eligible	0.0032%	31,227
East Asian	0.00223%	44,864

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: DRC2
Protein: p.Phe88Ser
Coding: c.263T>C
MANE Select: NM_033124
dbSNP: rs148153593
Type: single nucleotide variant
Location: chr12:48905076 (GRCh38)
Structure: AlphaFold pLDDT 83.21 · 1 PDB

Full DRC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: primary ciliary dyskinesia 27

Similar variants

CCDC65 p.Arg70Gln Uncertain significance ★★ ⚠ same condition
CCDC65 p.Glu110Lys Uncertain significance ★★ ⚠ same condition
CCDC65 p.Lys158Asn Uncertain significance ★★ ⚠ same condition
DRC2 p.Ala109Val Uncertain significance ★★ ⚠ same condition
DRC2 p.Ala114Pro Uncertain significance ★★ ⚠ same condition
DRC2 p.Arg118Cys Uncertain significance ★★ ⚠ same condition
DRC2 p.Arg294His Uncertain significance ★★ ⚠ same condition
DRC2 p.Arg315Gln Uncertain significance ★★ ⚠ same condition

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/drc2-p-phe88ser (accessed [today's date]).

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