Is ANKRD44 p.Pro110Leu (c.329C>T) pathogenic?

ANKRD44 p.Pro110Leu (c.329C>T) is classified Uncertain significance in ANKRD44 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-17). AlphaMissense: likely pathogenic (0.9939); Absent from gnomAD v4.1.

How common is ANKRD44 p.Pro110Leu (c.329C>T) in the general population?

ANKRD44 p.Pro110Leu (c.329C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ANKRD44 p.Pro110Leu (c.329C>T)?

AlphaMissense predicts likely pathogenic (score 0.9939) — an in-silico prediction, not a clinical call.

ANKRD44 p.Pro110Leu

c.329C>T · VCV4107501

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9939 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9939	likely pathogenic · top 8% in ANKRD44
REVEL	0.805	moderately pathogenic-leaning
SaProt	LLR -15.00	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 12	GERP 2.9, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 321 kb · p 8.9e-11 · regional, not allelic
Overall
CADD	29.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ANKRD44
Protein: p.Pro110Leu
Coding: c.329C>T
MANE Select: NM_001195144
Type: single nucleotide variant
Location: chr2:197125970 (GRCh38)
Gene constraint: LOEUF 0.365 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 90.57

Full ANKRD44 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ANKRD44 c.1317-1308T>C Likely pathogenic ★ same type
ANKRD44 p.Ala164Thr Uncertain significance ★ ⚠ same type
ANKRD44 p.Ala180Thr Uncertain significance ★ ⚠ same type
ANKRD44 p.Ala242Val Uncertain significance ★ ⚠ same type
ANKRD44 p.Ala246Val Uncertain significance ★ ⚠ same type
ANKRD44 p.Ala2Gly Uncertain significance ★ ⚠ same type
ANKRD44 p.Ala462Ser Uncertain significance ★ ⚠ same type
ANKRD44 p.Ala478Thr 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/ankrd44-p-pro110leu (accessed [today's date]).

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