Is CCDC172 p.Ser54Phe (c.161C>T) pathogenic?

CCDC172 p.Ser54Phe (c.161C>T) is classified Uncertain significance in CCDC172 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-06). AlphaMissense: likely benign (0.1166); Ultra-rare (popmax 0.0165%, mid).

How common is CCDC172 p.Ser54Phe (c.161C>T) in the general population?

CCDC172 p.Ser54Phe (c.161C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about CCDC172 p.Ser54Phe (c.161C>T)?

AlphaMissense predicts likely benign (score 0.1166) — an in-silico prediction, not a clinical call.

CCDC172 p.Ser54Phe

c.161C>T · rs1301538913 · VCV2557235

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1166 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1166	likely benign
REVEL	0.158	moderately benign-leaning
SaProt	LLR -7.89	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.51 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.51	GERP -0.8
Regional constraint	o/e 1.02	unconstrained · MANE · 54 kb · p 0.68 · regional, not allelic
Overall
CADD	16.05	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,062 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000372% 6/1,611,796 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
European (non-Finnish)	0.000424%	235,740

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: CCDC172
Protein: p.Ser54Phe
Coding: c.161C>T
MANE Select: NM_198515
dbSNP: rs1301538913
Type: single nucleotide variant
Location: chr10:116325384 (GRCh38)
Gene constraint: LOEUF 1.536 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.63

Full CCDC172 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC172 p.Ala75Asp Uncertain significance ★ ⚠ same type
CCDC172 p.Ala75Thr Uncertain significance ★ ⚠ same type
CCDC172 p.Arg33Ser Uncertain significance ★ ⚠ same type
CCDC172 p.Arg35Cys Uncertain significance ★ ⚠ same type
CCDC172 p.Asp114Asn Uncertain significance ★ ⚠ same type
CCDC172 p.Asp230Asn Uncertain significance ★ ⚠ same type
CCDC172 p.Gln100His Uncertain significance ★ ⚠ same type
CCDC172 p.Gln100Pro 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/ccdc172-p-ser54phe (accessed [today's date]).

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