Is KCND2 p.Ser472Phe (c.1415C>T) pathogenic?

KCND2 p.Ser472Phe (c.1415C>T) is classified Likely benign in KCND2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-12). AlphaMissense: likely benign (0.3214); Rare (popmax 0.279%, afr); Associated with Inborn genetic diseases.

What condition is associated with KCND2 p.Ser472Phe (c.1415C>T)?

KCND2 p.Ser472Phe (c.1415C>T) is associated with Inborn genetic diseases (ClinVar).

How common is KCND2 p.Ser472Phe (c.1415C>T) in the general population?

KCND2 p.Ser472Phe (c.1415C>T) is rare (popmax 0.279%, afr) (gnomAD).

What do computational predictors say about KCND2 p.Ser472Phe (c.1415C>T)?

AlphaMissense predicts likely benign (score 0.3214) — an in-silico prediction, not a clinical call.

KCND2 p.Ser472Phe

c.1415C>T · rs146058924 · VCV767427

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.3214 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.279%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3214	likely benign
REVEL	0.559	indeterminate
SaProt	LLR -7.98	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.9, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 15 kb · p 0.0014 · regional, not allelic
Overall
CADD	27.3	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 0.279% African / African-American · 209/74,998 alleles

Filtering AF 0.248% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.236%

Overall 0.0152% 246/1,613,624 alleles · rare exomes 117/1,461,404 · genomes 129/152,220 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.279%	359
Remaining individualsnot grpmax-eligible	0.032%	3,124
Admixed American	0.025%	4,000
South Asian	0.0011%	91,070
European (non-Finnish)	8.48e-05%	1,179,660

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: KCND2
Protein: p.Ser472Phe
Coding: c.1415C>T
MANE Select: NM_012281
dbSNP: rs146058924
Type: single nucleotide variant
Location: chr7:120742550 (GRCh38)
Gene constraint: LOEUF 0.428 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.28 · 16 PDB

Full KCND2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

KCND2 p.Pro403Leu Pathogenic/Likely pathogenic ★★ same condition
KCND2 p.Val404Met Pathogenic ★★ same condition
KCND2 p.Ala145Thr Uncertain significance ★★ ⚠ same condition
KCND2 p.Arg449Gln Uncertain significance ★★ ⚠ same condition
KCND2 p.Asp150Glu Uncertain significance ★★ same condition
KCND2 p.His77Arg Uncertain significance ★★ ⚠ same condition
KCND2 p.Lys217Arg Uncertain significance ★★ ⚠ same condition
KCND2 p.Met20Ile Uncertain significance ★★ ⚠ same condition

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/kcnd2-p-ser472phe (accessed [today's date]).

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