Is CCDC170 p.Val604Ile (c.1810G>A) pathogenic?

CCDC170 p.Val604Ile (c.1810G>A) is classified Conflicting classifications of pathogenicity in CCDC170 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-07-30). AlphaMissense: likely benign (0.0829); Common (popmax 49.8%, afr) — too common for a highly-penetrant pathogenic allele; Associated with CCDC170-related condition.

What condition is associated with CCDC170 p.Val604Ile (c.1810G>A)?

CCDC170 p.Val604Ile (c.1810G>A) is associated with CCDC170-related condition, estrogen resistance syndrome (ClinVar).

What do computational predictors say about CCDC170 p.Val604Ile (c.1810G>A)?

AlphaMissense predicts likely benign (score 0.0829) — an in-silico prediction, not a clinical call.

CCDC170 p.Val604Ile

Q: How common is CCDC170 p.Val604Ile (c.1810G>A) in the general population?

CCDC170 p.Val604Ile (c.1810G>A) is common (popmax 49.8%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1810G>A · rs6929137 · VCV155873

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0829 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 49.8%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

CCDC170-related condition

Computational evidence

Protein change
AlphaMissense	0.0829	likely benign
REVEL	0.044	moderately benign-leaning
SaProt	LLR -6.82	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 5	GERP 0.017, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 124 kb · p 0.5 · regional, not allelic
Overall
CADD	12.44	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 49.8% African / African-American · 37,349/74,924 alleles

Filtering AF 49.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 49.3%

Overall 32.8% 529,827/1,613,434 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	49.8%	2
Middle Eastern	39.5%	3
Ashkenazi Jewishnot grpmax-eligible	36.2%	3
Remaining individualsnot grpmax-eligible	34.4%	3
South Asian	33.3%	3
European (non-Finnish)	33%	3
East Asian	28.5%	4
Amishnot grpmax-eligible	26.4%	4
Admixed American	22.4%	4
Finnishnot grpmax-eligible	19%	5

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: CCDC170
Protein: p.Val604Ile
Coding: c.1810G>A
MANE Select: NM_025059
dbSNP: rs6929137
Type: single nucleotide variant
Location: chr6:151615542 (GRCh38)
Gene constraint: LOEUF 1.158 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.06
Residue 604: a UniProt-annotated variant site (in)

Full CCDC170 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CCDC170-related condition

Also linked: estrogen resistance syndrome

Similar variants

CCDC170 c.1710+1144T>G Uncertain significance same condition
CCDC170 c.*68A>C Uncertain significance same condition
CCDC170 c.*978A>G Uncertain significance same condition
CCDC170 p.Ala17Glu Uncertain significance ★ ⚠ same type
CCDC170 p.Ala17Val Uncertain significance ★ ⚠ same type
CCDC170 p.Ala246Ser Uncertain significance ★ ⚠ same type
CCDC170 p.Ala315Glu Uncertain significance ★ ⚠ same type
CCDC170 p.Ala331Val 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/ccdc170-p-val604ile (accessed [today's date]).

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