Is ANKRD33B p.Pro388Ser (c.1162C>T) pathogenic?

ANKRD33B p.Pro388Ser (c.1162C>T) is classified Uncertain significance in ANKRD33B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-14). AlphaMissense: likely benign (0.0743); Rare (popmax 0.208%, mid).

How common is ANKRD33B p.Pro388Ser (c.1162C>T) in the general population?

ANKRD33B p.Pro388Ser (c.1162C>T) is rare (popmax 0.208%, mid) (gnomAD).

What do computational predictors say about ANKRD33B p.Pro388Ser (c.1162C>T)?

AlphaMissense predicts likely benign (score 0.0743) — an in-silico prediction, not a clinical call.

ANKRD33B p.Pro388Ser

c.1162C>T · rs181259002 · VCV2219071

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0743 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.208%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0743	likely benign
REVEL	0.033	moderately benign-leaning
SaProt	LLR -6.52	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 -3.1	GERP -2.3
Regional constraint	o/e 0.96	unconstrained · MANE · 85 kb · p 0.32 · regional, not allelic
Overall
CADD	0.14	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 0.208% Middle Eastern · 8/3,852 alleles

Filtering AF 0.103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0754%

Overall 0.0168% 235/1,397,706 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.208%	482
Remaining individualsnot grpmax-eligible	0.043%	2,324
South Asian	0.0325%	3,073
European (non-Finnish)	0.0164%	6,115
Admixed American	0.00978%	10,224
African / African-American	0.00456%	21,942

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: ANKRD33B
Protein: p.Pro388Ser
Coding: c.1162C>T
MANE Select: NM_001164440
dbSNP: rs181259002
Type: single nucleotide variant
Location: chr5:10649790 (GRCh38)
Gene constraint: LOEUF 0.682 · pLI 0.70 (gnomAD)
Structure: AlphaFold pLDDT 67.74
Residue 388: the 'disordered' region

Full ANKRD33B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ANKRD33B p.Pro388Leu Uncertain significance ★ ⚠ same residue
ANKRD33B p.Asp301Asn Uncertain significance ★★ ⚠ same type
ANKRD33B p.Ala158Pro Uncertain significance ★ ⚠ same type
ANKRD33B p.Ala168Val Uncertain significance ★ ⚠ same type
ANKRD33B p.Ala214Val Uncertain significance ★ ⚠ same type
ANKRD33B p.Ala274Thr Uncertain significance ★ ⚠ same type
ANKRD33B p.Ala319Val Uncertain significance ★ ⚠ same type
ANKRD33B p.Ala348Val 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/ankrd33b-p-pro388ser (accessed [today's date]).

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