Is CCDC62 p.Pro449Arg (c.1346C>G) pathogenic?

CCDC62 p.Pro449Arg (c.1346C>G) is classified Uncertain significance in CCDC62 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-12). AlphaMissense: likely benign (0.099); Ultra-rare (popmax 0.045%, sas).

How common is CCDC62 p.Pro449Arg (c.1346C>G) in the general population?

CCDC62 p.Pro449Arg (c.1346C>G) is ultra-rare (popmax 0.045%, sas) (gnomAD).

What do computational predictors say about CCDC62 p.Pro449Arg (c.1346C>G)?

AlphaMissense predicts likely benign (score 0.099) — an in-silico prediction, not a clinical call.

CCDC62 p.Pro449Arg

c.1346C>G · rs749239981 · VCV2254135

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.099 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.045%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.099	likely benign
REVEL	0.013	strongly benign-leaning
SaProt	LLR -6.02	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 -0.36	GERP -3.6
Regional constraint	o/e 0.87	unconstrained · MANE · 49 kb · p 0.00021 · regional, not allelic
Overall
CADD	0.236	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.045% South Asian · 41/91,076 alleles

Filtering AF 0.0341% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0302%

Overall 0.00285% 46/1,613,980 alleles · ultra-rare exomes 44/1,461,880 · genomes 2/152,100 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.045%	2,221
Remaining individualsnot grpmax-eligible	0.008%	12,498

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: CCDC62
Protein: p.Pro449Arg
Coding: c.1346C>G
MANE Select: NM_201435
dbSNP: rs749239981
Type: single nucleotide variant
Location: chr12:122801492 (GRCh38)
Gene constraint: LOEUF 1.012 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.07
Residue 449: a UniProt-annotated variant site (in spgf67)

Full CCDC62 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC62 p.Gln364= Benign ★★ same type
CCDC62 p.Ala190Gly Uncertain significance ★ ⚠ same type
CCDC62 p.Ala271Glu Uncertain significance ★ ⚠ same type
CCDC62 p.Ala271Ser Uncertain significance ★ ⚠ same type
CCDC62 p.Ala322Asp Uncertain significance ★ ⚠ same type
CCDC62 p.Ala503Gly Uncertain significance ★ ⚠ same type
CCDC62 p.Ala6Ser Uncertain significance ★ ⚠ same type
CCDC62 p.Arg11Cys 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/ccdc62-p-pro449arg (accessed [today's date]).

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