Is ANKRD54 p.Arg92Ser (c.276G>T) pathogenic?

ANKRD54 p.Arg92Ser (c.276G>T) is classified Uncertain significance in ANKRD54 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-07). AlphaMissense: likely pathogenic (0.6144); Absent from gnomAD v4.1.

How common is ANKRD54 p.Arg92Ser (c.276G>T) in the general population?

ANKRD54 p.Arg92Ser (c.276G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ANKRD54 p.Arg92Ser (c.276G>T)?

AlphaMissense predicts likely pathogenic (score 0.6144) — an in-silico prediction, not a clinical call.

ANKRD54 p.Arg92Ser

c.276G>T · VCV3873862

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6144 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,407,506)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6144	likely pathogenic
REVEL	0.25	benign-leaning
SaProt	LLR -7.30	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.2	GERP 1.3, phastCons 0.15
Regional constraint	o/e 1.10	unconstrained · MANE · 326 bp · p 0.2 · regional, not allelic
Overall
CADD	18.36	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

No allele count reported in gnomAD v4.1 (AN 1,407,506). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ANKRD54
Protein: p.Arg92Ser
Coding: c.276G>T
MANE Select: NM_138797
Type: single nucleotide variant
Location: chr22:37843963 (GRCh38)
Gene constraint: LOEUF 1.126 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.74

Full ANKRD54 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ANKRD54 p.Leu163= Benign ★★ same type
ANKRD54 p.Ala134Thr Uncertain significance ★ ⚠ same type
ANKRD54 p.Ala233Val Uncertain significance ★ ⚠ same type
ANKRD54 p.Ala40Thr Uncertain significance ★ ⚠ same type
ANKRD54 p.Ala88Thr Uncertain significance ★ ⚠ same type
ANKRD54 p.Arg144Cys Uncertain significance ★ ⚠ same type
ANKRD54 p.Arg172Gln Uncertain significance ★ ⚠ same type
ANKRD54 p.Arg235His 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/ankrd54-p-arg92ser (accessed [today's date]).

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