Is CEP170 p.Pro611Ser (c.1831C>T) pathogenic?

CEP170 p.Pro611Ser (c.1831C>T) is classified Uncertain significance in CEP170 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-26). AlphaMissense: likely benign (0.0826); Very rare (popmax 0.0067%, afr).

How common is CEP170 p.Pro611Ser (c.1831C>T) in the general population?

CEP170 p.Pro611Ser (c.1831C>T) is very rare (popmax 0.0067%, afr) (gnomAD).

What do computational predictors say about CEP170 p.Pro611Ser (c.1831C>T)?

AlphaMissense predicts likely benign (score 0.0826) — an in-silico prediction, not a clinical call.

CEP170 p.Pro611Ser

c.1831C>T · rs764437775 · VCV3142636

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0826 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0067%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0826	likely benign
REVEL	0.055	moderately benign-leaning
SaProt	LLR -5.12	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 0.97	GERP -2.3, phastCons 1
Regional constraint	o/e 0.68	unconstrained · MANE · 20 kb · p 3.5e-09 · regional, not allelic
Overall
CADD	14.21	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 0.0067% African / African-American · 5/74,640 alleles

Filtering AF 0.00256% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00162%

Overall 0.000376% 6/1,594,258 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0067%	14,928
South Asian	0.00114%	87,364

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: CEP170
Protein: p.Pro611Ser
Coding: c.1831C>T
MANE Select: NM_014812
dbSNP: rs764437775
Type: single nucleotide variant
Location: chr1:243169640 (GRCh38)
Gene constraint: LOEUF 0.261 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 46.25 · 1 PDB
Residue 611: the 'disordered' region

Full CEP170 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CEP170 p.Val1524Met Uncertain significance ★★ ⚠ same type
CEP170 c.4319+9A>T Benign ★★ same type
CEP170 p.Met1275Val Benign ★★ same type
CEP170 p.Tyr1291= Benign/Likely benign ★★ same type
CEP170 c.195+1G>A Uncertain significance ★ same type
CEP170 p.Ala1163Val Uncertain significance ★ ⚠ same type
CEP170 p.Ala1310Thr Uncertain significance ★ ⚠ same type
CEP170 p.Ala1392Gly 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/cep170-p-pro611ser (accessed [today's date]).

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