Is CCDC91 p.Glu170Asp (c.510A>T) pathogenic?

CCDC91 p.Glu170Asp (c.510A>T) is classified Uncertain significance in CCDC91 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-18). AlphaMissense: likely pathogenic (0.7198); Very rare (popmax 0.00345%, sas).

How common is CCDC91 p.Glu170Asp (c.510A>T) in the general population?

CCDC91 p.Glu170Asp (c.510A>T) is very rare (popmax 0.00345%, sas) (gnomAD).

What do computational predictors say about CCDC91 p.Glu170Asp (c.510A>T)?

AlphaMissense predicts likely pathogenic (score 0.7198) — an in-silico prediction, not a clinical call.

CCDC91 p.Glu170Asp

c.510A>T · VCV3828942

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7198 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00345%, sas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7198	likely pathogenic
REVEL	0.106	moderately benign-leaning
SaProt	LLR -10.68	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.6	GERP -0.48, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 292 kb · p 0.81 · regional, not allelic
Overall
CADD	22.9	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 0.00345% South Asian · 3/86,864 alleles

Filtering AF 0.000917% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000454%

Overall 0.000209% 3/1,437,460 alleles · very rare

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: CCDC91
Protein: p.Glu170Asp
Coding: c.510A>T
MANE Select: NM_018318
Type: single nucleotide variant
Location: chr12:28307683 (GRCh38)
Gene constraint: LOEUF 1.084 · pLI 0.06 (gnomAD)
Structure: AlphaFold pLDDT 76.04 · 1 PDB

Full CCDC91 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC91 p.Asp121Gly Benign ★★ same type
CCDC91 p.Gln403Lys Benign ★★ ⚠ same type
CCDC91 p.Ala127Thr Uncertain significance ★ ⚠ same type
CCDC91 p.Ala181Thr Uncertain significance ★ ⚠ same type
CCDC91 p.Ala209Thr Uncertain significance ★ ⚠ same type
CCDC91 p.Ala219Thr Uncertain significance ★ ⚠ same type
CCDC91 p.Ala28Ser Uncertain significance ★ ⚠ same type
CCDC91 p.Ala334Gly 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/ccdc91-p-glu170asp (accessed [today's date]).

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