Is ANKRD55 p.Ser376Pro (c.1126T>C) pathogenic?

ANKRD55 p.Ser376Pro (c.1126T>C) is classified Likely benign in ANKRD55 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-03-01). AlphaMissense: likely benign (0.1332); Rare (popmax 0.818%, nfe).

How common is ANKRD55 p.Ser376Pro (c.1126T>C) in the general population?

ANKRD55 p.Ser376Pro (c.1126T>C) is rare (popmax 0.818%, nfe) (gnomAD).

What do computational predictors say about ANKRD55 p.Ser376Pro (c.1126T>C)?

AlphaMissense predicts likely benign (score 0.1332) — an in-silico prediction, not a clinical call.

ANKRD55 p.Ser376Pro

c.1126T>C · rs77017041 · VCV719615

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1332 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.818%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1332	likely benign
REVEL	0.171	moderately benign-leaning
SaProt	LLR -7.12	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 9.2	GERP 0.58, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 71 kb · p 0.67 · regional, not allelic
Overall
CADD	22.5	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 0.818% European (non-Finnish) · 9,534/1,165,674 alleles

Filtering AF 0.804% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.798%

Overall 0.674% 10,650/1,579,604 alleles · rare exomes 9,948/1,427,390 · genomes 702/152,214 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.818%	122
Finnishnot grpmax-eligible	0.685%	146
Remaining individualsnot grpmax-eligible	0.597%	168
South Asian	0.155%	645
Ashkenazi Jewishnot grpmax-eligible	0.152%	657
African / African-American	0.119%	837
Admixed American	0.113%	888
Middle Eastern	0.0684%	1,461

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: ANKRD55
Protein: p.Ser376Pro
Coding: c.1126T>C
MANE Select: NM_024669
dbSNP: rs77017041
Type: single nucleotide variant
Location: chr5:56111622 (GRCh38)
Gene constraint: LOEUF 0.843 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.43

Full ANKRD55 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ANKRD55 p.Ala239Glu Uncertain significance ★★ ⚠ same type
ANKRD55 p.Gly242Ala Uncertain significance ★★ same type
ANKRD55 p.Ala241= Benign ★★ same type
ANKRD55 p.Glu279Lys Benign/Likely benign ★★ same type
ANKRD55 c.1723+1G>A Uncertain significance ★ same type
ANKRD55 p.Ala35Gly Uncertain significance ★ ⚠ same type
ANKRD55 p.Ala360Thr Uncertain significance ★ ⚠ same type
ANKRD55 p.Ala462Pro 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/ankrd55-p-ser376pro (accessed [today's date]).

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