CCDC174 p.Val348=

Q: Is CCDC174 p.Val348= (c.1044C>A) pathogenic?

CCDC174 p.Val348= (c.1044C>A) is classified Benign/Likely benign in CCDC174 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2022-05-17). Common (popmax 5.21%, afr) — too common for a highly-penetrant pathogenic allele; Associated with severe hypotonia-psychomotor developmental delay-strabismus-cardiac septal defect syndrome.

Q: What condition is associated with CCDC174 p.Val348= (c.1044C>A)?

CCDC174 p.Val348= (c.1044C>A) is associated with severe hypotonia-psychomotor developmental delay-strabismus-cardiac septal defect syndrome (ClinVar).

Q: How common is CCDC174 p.Val348= (c.1044C>A) in the general population?

CCDC174 p.Val348= (c.1044C>A) is common (popmax 5.21%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

Q: How is Severe hypotonia-psychomotor developmental delay-strabismus-cardiac septal defect syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.1044C>A · rs17040078 · VCV783368

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 5.21%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

severe hypotonia-psychomotor developmental delay-strabismus-cardiac septal defect syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.082	GERP -3.9, phastCons 0.74
Overall
CADD	5.463	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.21% African / African-American · 3,898/74,748 alleles

Filtering AF 5.08% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.02%

Overall 0.276% 4,439/1,611,200 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.21%	19
Middle Eastern	0.364%	275
Admixed American	0.345%	290
Remaining individualsnot grpmax-eligible	0.343%	292
Ashkenazi Jewishnot grpmax-eligible	0.0542%	1,844
South Asian	0.0111%	9,043
European (non-Finnish)	0.00636%	15,723

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: CCDC174
Protein: p.Val348=
Coding: c.1044C>A
MANE Select: NM_016474
dbSNP: rs17040078
Type: single nucleotide variant
Location: chr3:14670025 (GRCh38)
Gene constraint: LOEUF 0.926 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.79
Residue 348: the 'disordered' region

Full CCDC174 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

severe hypotonia-psychomotor developmental delay-strabismus-cardiac septal defect syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Severe hypotonia-psychomotor developmental delay-strabismus-cardiac septal defect syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Neonatal

Similar variants

CCDC174 p.Asp395His Uncertain significance ★★ ⚠ same condition
CCDC174 p.Phe29Ser Uncertain significance ★★ ⚠ same condition
CCDC174 p.Pro158Ser Uncertain significance ★★ ⚠ same condition
CCDC174 c.308-55C>A Benign ★★ same condition
CCDC174 c.485+83C>G Benign ★★ same condition
CCDC174 c.725-13A>G Benign ★★ same condition
CCDC174 p.Pro392= Benign ★★ same condition
CCDC174 p.Arg174Leu 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/ccdc174-p-val348 (accessed [today's date]).

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