Is CCDC73 p.Arg42Cys (c.124C>T) pathogenic?

CCDC73 p.Arg42Cys (c.124C>T) is classified Uncertain significance in CCDC73 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-21). AlphaMissense: ambiguous (0.3417); Very rare (popmax 0.00342%, sas).

How common is CCDC73 p.Arg42Cys (c.124C>T) in the general population?

CCDC73 p.Arg42Cys (c.124C>T) is very rare (popmax 0.00342%, sas) (gnomAD).

What do computational predictors say about CCDC73 p.Arg42Cys (c.124C>T)?

AlphaMissense predicts ambiguous (score 0.3417) — an in-silico prediction, not a clinical call.

CCDC73 p.Arg42Cys

c.124C>T · VCV3264287

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3417 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00342%, sas)

Computational evidence

Protein change
AlphaMissense	0.3417	ambiguous
REVEL	0.406	indeterminate
SaProt	LLR -9.50	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 157 kb · p 5.1e-05 · regional, not allelic
Overall
CADD	31.0	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 0.00342% South Asian · 3/87,594 alleles

Filtering AF 0.002% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00176%

Overall 0.00275% 44/1,598,338 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00968%	10,326
South Asiangrpmax	0.00342%	29,198
European (non-Finnish)	0.00281%	35,575
Finnishnot grpmax-eligible	0.00157%	63,856
African / African-American	0.00135%	73,978

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: CCDC73
Protein: p.Arg42Cys
Coding: c.124C>T
MANE Select: NM_001008391
Type: single nucleotide variant
Location: chr11:32760120 (GRCh38)
Gene constraint: LOEUF 1.103 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 54.16

Full CCDC73 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC73 p.Arg42His Uncertain significance ★ ⚠ same residue
CCDC73 p.Ala220Glu Uncertain significance ★ ⚠ same type
CCDC73 p.Ala221Val Uncertain significance ★ ⚠ same type
CCDC73 p.Ala614Val Uncertain significance ★ ⚠ same type
CCDC73 p.Ala717Val Uncertain significance ★ ⚠ same type
CCDC73 p.Ala789Thr Uncertain significance ★ ⚠ same type
CCDC73 p.Ala88Thr Uncertain significance ★ ⚠ same type
CCDC73 p.Ala974Asp 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/ccdc73-p-arg42cys (accessed [today's date]).

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