Is DIPK1A p.Ser93Pro (c.277T>C) pathogenic?

DIPK1A p.Ser93Pro (c.277T>C) is classified Uncertain significance in DIPK1A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-10). AlphaMissense: likely pathogenic (0.9426); Very rare (popmax 0.000781%, nfe).

How common is DIPK1A p.Ser93Pro (c.277T>C) in the general population?

DIPK1A p.Ser93Pro (c.277T>C) is very rare (popmax 0.000781%, nfe) (gnomAD).

What do computational predictors say about DIPK1A p.Ser93Pro (c.277T>C)?

AlphaMissense predicts likely pathogenic (score 0.9426) — an in-silico prediction, not a clinical call.

DIPK1A p.Ser93Pro

c.277T>C · VCV3502070

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9426 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000781%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9426	likely pathogenic
REVEL	0.32	indeterminate
SaProt	LLR -8.84	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.7, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 118 kb · p 3.1e-05 · regional, not allelic
Overall
CADD	26.6	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 0.000781% European (non-Finnish) · 9/1,152,568 alleles

Filtering AF 0.000367% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000266%

Overall 0.000637% 9/1,412,256 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: DIPK1A
Protein: p.Ser93Pro
Coding: c.277T>C
MANE Select: NM_001006605
Type: single nucleotide variant
Location: chr1:92850868 (GRCh38)
Gene constraint: LOEUF 1.244 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.20

Full DIPK1A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

RPL5 c.4-1G>A Likely pathogenic ★★ same type
RPL5 c.527+1G>T Pathogenic/Likely pathogenic ★★ same type
RPL5 c.74-1G>A Pathogenic/Likely pathogenic ★★ same type
RPL5 p.Arg179Ter Pathogenic/Likely pathogenic ★★ same type
RPL5 p.Arg23Ter Pathogenic ★★ same type
RPL5 p.Arg248Ter Pathogenic/Likely pathogenic ★★ same type
RPL5 p.Arg24Ter Pathogenic/Likely pathogenic ★★ same type
RPL5 p.Gln39Ter Pathogenic/Likely pathogenic ★★ 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/dipk1a-p-ser93pro (accessed [today's date]).

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