Is ANKRD2 p.Pro119Leu (c.356C>T) pathogenic?

ANKRD2 p.Pro119Leu (c.356C>T) is classified Benign/Likely benign in ANKRD2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2022-08-01). AlphaMissense: likely benign (0.1268); Rare (popmax 0.759%, nfe).

How common is ANKRD2 p.Pro119Leu (c.356C>T) in the general population?

ANKRD2 p.Pro119Leu (c.356C>T) is rare (popmax 0.759%, nfe) (gnomAD).

What do computational predictors say about ANKRD2 p.Pro119Leu (c.356C>T)?

AlphaMissense predicts likely benign (score 0.1268) — an in-silico prediction, not a clinical call.

ANKRD2 p.Pro119Leu

c.356C>T · rs36020819 · VCV774685

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1268 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.759%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1268	likely benign
REVEL	0.184	benign-leaning
SaProt	LLR -10.25	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.4, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 11 kb · p 0.092 · regional, not allelic
Overall
CADD	27.9	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P146L vs ClinVar P119L) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.759% European (non-Finnish) · 8,840/1,165,396 alleles

Filtering AF 0.745% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.74%

Overall 0.629% 9,967/1,585,216 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.759%	132
Finnishnot grpmax-eligible	0.73%	137
Remaining individualsnot grpmax-eligible	0.669%	150
Amishnot grpmax-eligible	0.658%	152
Admixed American	0.24%	417
African / African-American	0.0953%	1,049
Middle Eastern	0.0828%	1,207
South Asian	0.0479%	2,089
Ashkenazi Jewishnot grpmax-eligible	0.0276%	3,629

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: ANKRD2
Protein: p.Pro119Leu
Coding: c.356C>T
MANE Select: NM_001346793
dbSNP: rs36020819
Type: single nucleotide variant
Location: chr10:97578505 (GRCh38)
Gene constraint: LOEUF 1.426 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.30
Residue 119: the 'may mediate interaction with pml, p53/tp53 and ybx1' region

Full ANKRD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ANKRD2 p.Ala285= Benign ★★ same type
ANKRD2 p.Pro6Arg Benign ★★ same type
ANKRD2 p.Ala10Val Uncertain significance ★ ⚠ same type
ANKRD2 p.Ala128Val Uncertain significance ★ ⚠ same type
ANKRD2 p.Ala12Thr Uncertain significance ★ ⚠ same type
ANKRD2 p.Ala311Val Uncertain significance ★ ⚠ same type
ANKRD2 p.Arg100Pro Uncertain significance ★ ⚠ same type
ANKRD2 p.Arg155Gln 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/ankrd2-p-pro119leu (accessed [today's date]).

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